Venom-Derived Neurotoxins Targeting Nicotinic Acetylcholine Receptors
Abstract
:1. Introduction
1.1. Structural Features of Nicotinic AChRs for Ligand Interaction
1.2. Importance of Nicotinic Acetylcholine Receptors in Physiology and Pathology
2. Snail Venoms as a Source of Toxins Acting on Acetylcholine Receptors
2.1. α3/5 Conotoxins
2.2. α4/3 Conotoxins
2.3. α4/4 Conotoxins
2.4. α4/6 Conotoxins
2.5. α4/7 Conotoxins
2.6. Therapeutic Potential of α-Conotoxins
α-Conotoxin | Species | Target and IC50 / Ki | Reference | UniProt/PDB |
---|---|---|---|---|
Ac1.1a | C. achatinus | m(α1)2β1δγ (IC50 = 36 nM) | [27] | P0CAQ4/n.d. |
Ac1.1b | C. achatinus | m(α1)2β1δγ (IC50 = 26 nM) | [27] | P0CAQ5/n.d. |
CIA | C. catus | r(α1)2β1δγ (IC50 = 5.7 nM) rα3β2 (IC50 = 2.06 μM) | [31] | D4HPD6/n.d. |
GI | C. geographus | Torpedo californica (IC50 α/γ site = 4.5 nM) (IC50 α/δ site = 87 nM) m(α1)2β1δγ (IC50 α/δ site = 1.3 nM) (IC50 α/γ site = 60 μM) rα9α10 (IC50 = 9.35 μM) | [29,30] | P01519/1XGA |
MI | C. magus | m(α1)2β1δγ (IC50 = 0.4 nM) | [26] | P01521/n.d. |
SIA | C. striatus | m(α1)2β1δγ (IC50 = 2.6 nM) (IC50 = 2.3 μM) | [28] | P28878/n.d. |
SII | C. striatus | m(α1)2β1δγ (IC50 = 18 μM) | [28] | P28879/6OTB |
ImI | C.imperialis | hα3β2 (IC50 = 40.8 nM) hα3β4 (IC50 = 3.39 μM) hα7 (IC50 = 595 nM) rα7 (IC50 = 191 nM) rα7 (IC50 = 69.3 nM) | [34,81] | P50983/1CNL |
ImII | C.imperialis | h(α1)2β1δε (IC50 = 1.06 μM) hα3β2 (IC50 = 9.61 μM) hα7 (IC50 = 571 nM) rα7 (IC50 = 441 nM) | [34,81] | Q8I6R5/n.d. |
RgIA | C. regius | rα9α10 (IC50 = 4.55–5.19 nM) rα7 (IC50 = 4.66 μM) | [82] | P0C1D0/2JUT |
BuIA | C. bullatus | rα6/α3β2 (IC50 = 0.3 nM) rα6/α3β2β3 (IC50 = 0.46 nM) rα6/α3β4 (IC50 = 1.5–2.1 nM) rα2β4 (IC50 = 121 nM) rα3β2 (IC50 = 5.7 nM) rα3β4 (IC50 = 28 nM) rα4β4 (IC50 = 70 nM) rα7 (IC50 = 272 nM) | [37,39] | P69657/2I28 |
EIIA | C. ermineus | Torpedo (Ki = 0.46–105 nM) α7-5HT3 (Ki >>1000 nM) α3β2 (Ki >>1000 nM) α4β2 (Ki >>1000 nM) | [40] | D4HRK4/n.d. |
PIB | C. purpurascens | m(α1)2β1δε (IC50 = 36 nM) m(α1)2β1δγ (IC50 = 45 nM) | [83] | P0C351/n.d. |
AuIB | C. aulicus | α3β2/α3β4 (intracardiac ganglia) (IC50 = 1.2 nM) rα3β4 (recombinant) (IC50 = 750–966 nM) | [84,85] | P56640/1MXN |
ViIA | C. virgo | rα3β2 (IC50 = 845.5 nM) | [42] | F5C0A0/n.d. |
VnIB | C. ventricosus | rα6β4 (IC50 = 12 nM) rα6/α3β4 (IC50 = 18 nM) rα3β4 (IC50 = 320 nM) rα6/α3β2β3 (IC50 = 4000 nM) hα6/α3β4 (IC50 = 5.3 nM) | [43] | A0A4P8XV20/n.d. |
TxID | C. textile | rα3β4 (IC50 = 12.5 nM) rα6/α3β4 (IC50 = 94 nM) | [64] | K8DWB5/n.d. |
AnIB | C. anemone | rα3β2 (IC50 = 0.3 nM) rα7 (IC50 = 76 nM) | [45] | P0C1V7/n.d. |
ArIA | C. arenatus | rα7 (IC50 = 6 nM) rα3β2 (IC50 = 18 nM) | [46] | P0C8R2/n.d. |
ArIB | C. arenatus | rα7 (IC50 = 1.8 nM) rα6/α3β2β3 (IC50 = 6.45 nM) rα3β2 (IC50 = 60.1 nM) | [46] | P0C8R2/n.d. |
CIB | C.catus | rα3β2 (IC50 = 128.9 nM) rα7 (IC50 = 1.51 μM) | [24] | P0DPT2/n.d. |
EI | C. ermineus | m(α1)2β1δε (IC50(1) = 9.4 nM) (IC50(2) = 280 nM) Torpedo (IC50(1) = 0.41 nM) (IC50(2) = 190 nM) | [86] | P50982/1K64 |
GIC | C. geographus | hα3β2 (IC50 = 1.1 nM) hα3β4 (IC50 = 755 nM) hα4β2 (IC50 = 309 nM) | [87] | Q86RB2/1UL2 |
GID | C. geographus | rα3β2 (IC50 = 3.1 nM) rα7 (IC50 = 4.5 nM) rα4β2 (IC50 = 152 nM) | [88,89] | P60274/1MTQ |
Lo1a | C. longurionis | α7 (IC50 = 3.24 μM) | [50] | X1WB75/2MD6 |
LsIA | C. limpusi | α3β2 (IC50 = 10 nM) α3α5β2 (IC50 = 31 nM) α7 (IC50 = 10 nM) | [51] | P0DL68/n.d. |
LtIA | C. litteratus | α3β2 (IC50 = 9.8 nM) α6/α3β2β3 (IC50 = 84.4 nM) α6/α3β4 (IC50 = 6 μM) | [90] | Q2I2R8/n.d. |
Lt1.3 | C. litteratus | rα3β2 (IC50 = 44.8 nM) | [52] | n.d. |
LvIA | C. lividus | α3β2 (IC50 = 8.7 nM) α6/α3β2β3 (IC50 = 108 nM) α6/α3β4 (IC50 = 121 nM) α3β4 (IC50 = 148 nM) α7 (IC50 = 3 μM) hα3β2 (IC50 = 17.5 nM) hα6/α3β2β3 (IC50 = 5.34 μM) | [53] | L8BU87/2MDQ |
MII | C. magus | α6/α3β2β3 (IC50 = 0.4 nM) α3β2 (IC50 = 0.5/3.7 nM) | [55,56,91] | P56636/1M2C |
Mr1.7 | C. marmoreus | rα3β2 (IC50 = 53.1 nM) rα9α10 (IC50 = 185.7 nM) rα6/α3β2β3 (IC50 = 284.2 nM) | [57] | F6LPN3/n.d. |
PeIA | C. pergrandis | rα9/α10 (IC50 = 6.9 nM) rα7 (IC50 = 1.8 μM) rα3β2 (IC50 = 23 nM) rα3β4 (IC50 = 480 nM) | [92] | Q1L777/n.d. |
PnIA | C. pennaceus | rα3β2 (IC50 = 9.56 nM) rα7 (IC50 = 252 nM) | [61] | P50984/1PEN |
RegIIA | C. regius | rα3β4 (IC50 = 97 nM) rα3β2 (IC50 = 33 nM) hα7 (IC50 = 103 nM) | [93] | P85013/n.d. |
TxIB | C. textile | rα6/α3β2β3 (IC50 = 28 nM) | [64] | K4RNX9/2LZ5 |
Vc1.1 | C. victoriae | rα9α10 (IC50 = 109 nM) hα9α10 (IC50 = 549 nM) rα6/α3β2β3 (IC50 = 140 nM) rα3β4 (IC50 = 4.2 μM) rα3β2 (IC50 = 7.3 μM) | [66,94] | P69747/2H8S |
3. Snake Venoms as a Source of Toxins Acting on Acetylcholine Receptors
3.1. Long-Chain Three-Finger α-NTXs
3.2. Short-Chain Three-Finger α-Neurotoxins
3.3. Dimeric Toxins
3.4. Non-Conventional Toxins
3.5. Toxins with Unique Structure
4. Peptides of Spider Venom Origin as Potential Ligands Acting on nAChRs
5. Peptides of Scorpion Venom Origin as Potential Ligands Acting on nAChRs
6. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
- Albuquerque, E.X.; Pereira, E.F.R.; Alkondon, M.; Rogers, S.W. Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function. Physiol. Rev. 2009, 89, 73–120. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Changeux, J.-P. Discovery of the First Neurotransmitter Receptor: The Acetylcholine Nicotinic Receptor. Biomolecules 2020, 10, 547. [Google Scholar] [CrossRef] [Green Version]
- Millar, N.S.; Gotti, C. Diversity of Vertebrate Nicotinic Acetylcholine Receptors. Neuropharmacology 2009, 56, 237–246. [Google Scholar] [CrossRef] [Green Version]
- Scholze, P.; Huck, S. The A5 Nicotinic Acetylcholine Receptor Subunit Differentially Modulates A4β2* and A3β4* Receptors. Front. Synaptic Neurosci. 2020, 12, 54. [Google Scholar] [CrossRef]
- Boorman, J.P.; Beato, M.; Groot-Kormelink, P.J.; Broadbent, S.D.; Sivilotti, L.G. The Effects of Β3 Subunit Incorporation on the Pharmacology and Single Channel Properties of Oocyte-Expressed Human A3β4 Neuronal Nicotinic Receptors. J. Biol. Chem. 2003, 278, 44033–44040. [Google Scholar] [CrossRef] [Green Version]
- Murray, T.A.; Bertrand, D.; Papke, R.L.; George, A.A.; Pantoja, R.; Srinivasan, R.; Liu, Q.; Wu, J.; Whiteaker, P.; Lester, H.A.; et al. A7β2 Nicotinic Acetylcholine Receptors Assemble, Function, and Are Activated Primarily via Their A7-A7 Interfaces. Mol. Pharmacol. 2012, 81, 175. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Plazas, P.V.; Katz, E.; Gomez-Casati, M.E.; Bouzat, C.; Elgoyhen, A.B. Stoichiometry of the A9α10 Nicotinic Cholinergic Receptor. J. Neurosci. 2005, 25, 10905. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gharpure, A.; Noviello, C.M.; Hibbs, R.E. Progress in Nicotinic Receptor Structural Biology. Neuropharmacology 2020, 171, 108086. [Google Scholar] [CrossRef] [PubMed]
- Karlin, A. A Touching Picture of Nicotinic Binding. Neuron 2004, 41, 841–842. [Google Scholar] [CrossRef] [Green Version]
- Kumbhare, D.; Palys, V.; Toms, J.; Wickramasinghe, C.S.; Amarasinghe, K.; Manic, M.; Hughes, E.; Holloway, K.L. Nucleus Basalis of Meynert Stimulation for Dementia: Theoretical and Technical Considerations. Front. Neurosci. 2018, 12, 614. [Google Scholar] [CrossRef] [PubMed]
- Govind, A.P.; Vezina, P.; Green, W.N. Nicotine-Induced Upregulation of Nicotinic Receptors: Underlying Mechanisms and Relevance to Nicotine Addiction. Biochem. Pharmacol. 2009, 78, 756–765. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Carbone, A.-L.; Moroni, M.; Groot-Kormelink, P.-J.; Bermudez, I. Pentameric Concatenated (A4)2(Β2)3 and (A4)3(Β2)2 Nicotinic Acetylcholine Receptors: Subunit Arrangement Determines Functional Expression. Br. J. Pharmacol. 2009, 156, 970–981. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- McGranahan, T.M.; Patzlaff, N.E.; Grady, S.R.; Heinemann, S.F.; Booker, T.K. A4β2 Nicotinic Acetylcholine Receptors on Dopaminergic Neurons Mediate Nicotine Reward and Anxiety Relief. J. Neurosci. 2011, 31, 10891. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- McIntosh, J.M.; Absalom, N.; Chebib, M.; Elgoyhen, A.B.; Vincler, M. Alpha9 Nicotinic Acetylcholine Receptors and the Treatment of Pain. Biochem. Pharmacol. 2009, 78, 693–702. [Google Scholar] [CrossRef] [Green Version]
- Del Bufalo, A.; Cesario, A.; Salinaro, G.; Fini, M.; Russo, P. Alpha9 Alpha10 Nicotinic Acetylcholine Receptors as Target for the Treatment of Chronic Pain. Curr. Pharm. Des. 2014, 20, 6042–6047. [Google Scholar] [CrossRef]
- Hone, A.J.; McIntosh, J.M. Nicotinic Acetylcholine Receptors in Neuropathic and Inflammatory Pain. FEBS Lett. 2018, 592, 1045–1062. [Google Scholar] [CrossRef] [Green Version]
- Bencherif, M.; Lippiello, P.M.; Lucas, R.; Marrero, M.B. Alpha7 Nicotinic Receptors as Novel Therapeutic Targets for Inflammation-Based Diseases. Cell. Mol. Life Sci. 2011, 68, 931–949. [Google Scholar] [CrossRef] [Green Version]
- Winek, K.; Soreq, H.; Meisel, A. Regulators of Cholinergic Signaling in Disorders of the Central Nervous System. J. Neurochem. 2021. [Google Scholar] [CrossRef]
- Dineley, K.T.; Pandya, A.A.; Yakel, J.L. Nicotinic ACh Receptors as Therapeutic Targets in CNS Disorders. Trends Pharmacol. Sci. 2015, 36, 96–108. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Quik, M.; Zhang, D.; McGregor, M.; Bordia, T. Alpha7 Nicotinic Receptors as Therapeutic Targets for Parkinson’s Disease. Biochem. Pharmacol. 2015, 97, 399–407. [Google Scholar] [CrossRef] [Green Version]
- Pennington, M.W.; Czerwinski, A.; Norton, R.S. Peptide Therapeutics from Venom: Current Status and Potential. Bioorgan. Med. Chem. 2018, 26, 2738–2758. [Google Scholar] [CrossRef] [PubMed]
- Jin, A.-H.; Muttenthaler, M.; Dutertre, S.; Himaya, S.W.A.; Kaas, Q.; Craik, D.J.; Lewis, R.J.; Alewood, P.F. Conotoxins: Chemistry and Biology. Chem. Rev. 2019, 119, 11510–11549. [Google Scholar] [CrossRef] [PubMed]
- Abraham, N.; Lewis, R.J. Neuronal Nicotinic Acetylcholine Receptor Modulators from Cone Snails. Mar. Drugs 2018, 16, 208. [Google Scholar] [CrossRef] [Green Version]
- Giribaldi, J.; Dutertre, S. α-Conotoxins to Explore the Molecular, Physiological and Pathophysiological Functions of Neuronal Nicotinic Acetylcholine Receptors. Neurosci. Lett. 2018, 679, 24–34. [Google Scholar] [CrossRef] [PubMed]
- McIntosh, J.M.; Santos, A.D.; Olivera, B.M. Conus Peptides Targeted to Specific Nicotinic Acetylcholine Receptor Subtypes. Annu. Rev. Biochem. 1999, 68, 59–88. [Google Scholar] [CrossRef]
- Jacobsen, R.B.; DelaCruz, R.G.; Grose, J.H.; McIntosh, J.M.; Yoshikami, D.; Olivera, B.M. Critical Residues Influence the Affinity and Selectivity of α-Conotoxin MI for Nicotinic Acetylcholine Receptors. Biochemistry 1999, 38, 13310–13315. [Google Scholar] [CrossRef]
- Liu, L.; Chew, G.; Hawrot, E.; Chi, C.; Wang, C. Two Potent A3/5 Conotoxins from Piscivorous Conus Achatinus. Acta Biochim. Biophys. Sin. 2007, 39, 438–444. [Google Scholar] [CrossRef] [Green Version]
- Groebe, D.R.; Dumm, J.M.; Levitan, E.S.; Abramson, S.N. Alpha-Conotoxins Selectively Inhibit One of the Two Acetylcholine Binding Sites of Nicotinic Receptors. Mol. Pharmacol. 1995, 48, 105. [Google Scholar]
- Groebe, D.R.; Gray, W.R.; Abramson, S.N. Determinants Involved in the Affinity of α-Conotoxins GI and SI for the Muscle Subtype of Nicotinic Acetylcholine Receptors. Biochemistry 1997, 36, 6469–6474. [Google Scholar] [CrossRef]
- Ning, J.; Li, R.; Ren, J.; Zhangsun, D.; Zhu, X.; Wu, Y.; Luo, S. Alanine-Scanning Mutagenesis of α-Conotoxin GI Reveals the Residues Crucial for Activity at the Muscle Acetylcholine Receptor. Mar. Drugs 2018, 16, 507. [Google Scholar] [CrossRef] [Green Version]
- Giribaldi, J.; Wilson, D.; Nicke, A.; El Hamdaoui, Y.; Laconde, G.; Faucherre, A.; Moha Ou Maati, H.; Daly, N.L.; Enjalbal, C.; Dutertre, S. Synthesis, Structure and Biological Activity of CIA and CIB, Two α-Conotoxins from the Predation-Evoked Venom of Conus Catus. Toxins 2018, 10, 222. [Google Scholar] [CrossRef] [Green Version]
- Ramilo, C.A.; Zafaralla, G.C.; Nadasdi, L.; Hammerland, L.G.; Yoshikami, D.; Gray, W.R.; Kristipati, R.; Ramachandran, J.; Miljanich, G. Novel .Alpha.- and .Omega.-Conotoxins and Conus Striatus Venom. Biochemistry 1992, 31, 9919–9926. [Google Scholar] [CrossRef] [PubMed]
- Quiram, P.A.; Sine, S.M. Structural Elements in α-Conotoxin ImI Essential for Binding to Neuronal A7 Receptors. J. Biol. Chem. 1998, 273, 11007–11011. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ellison, M.; McIntosh, J.M.; Olivera, B.M. α-Conotoxins ImI and ImII: Similar A7 nicotinic receptor antagonists act at different sites. J. Biol. Chem. 2003, 278, 757–764. [Google Scholar] [CrossRef] [Green Version]
- Ellison, M.; Feng, Z.-P.; Park, A.J.; Zhang, X.; Olivera, B.M.; McIntosh, J.M.; Norton, R.S. α-RgIA, a Novel Conotoxin That Blocks the A9α10 NAChR: Structure and Identification of Key Receptor-Binding Residues. J. Mol. Biol. 2008, 377, 1216–1227. [Google Scholar] [CrossRef] [Green Version]
- Chhabra, S.; Belgi, A.; Bartels, P.; van Lierop, B.J.; Robinson, S.D.; Kompella, S.N.; Hung, A.; Callaghan, B.P.; Adams, D.J.; Robinson, A.J.; et al. Dicarba Analogues of α-Conotoxin RgIA. Structure, Stability, and Activity at Potential Pain Targets. J. Med. Chem. 2014, 57, 9933–9944. [Google Scholar] [CrossRef] [PubMed]
- Azam, L.; Dowell, C.; Watkins, M.; Stitzel, J.A.; Olivera, B.M.; McIntosh, J.M. α-Conotoxin BuIA, a Novel Peptide from Conus Bullatus, Distinguishes among Neuronal Nicotinic Acetylcholine Receptors. J. Biol. Chem. 2005, 280, 80–87. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, H.-W.; McIntosh, J.M. A6 NAChR Subunit Residues That Confer α-Conotoxin BuIA Selectivity. FASEB J. 2012, 26, 4102–4110. [Google Scholar] [CrossRef] [Green Version]
- Azam, L.; Maskos, U.; Changeux, J.-P.; Dowell, C.D.; Christensen, S.; De Biasi, M.; McIntosh, J.M. α-Conotoxin BuIA[T5A;P6O]: A Novel Ligand That Discriminates between A6ß4 and A6ß2 Nicotinic Acetylcholine Receptors and Blocks Nicotine-Stimulated Norepinephrine Release. FASEB J. 2010, 24, 5113–5123. [Google Scholar] [CrossRef]
- Quinton, L.; Servent, D.; Girard, E.; Molgó, J.; Le Caer, J.-P.; Malosse, C.; Haidar, E.A.; Lecoq, A.; Gilles, N.; Chamot-Rooke, J. Identification and Functional Characterization of a Novel α-Conotoxin (EIIA) from Conus Ermineus. Anal. Bioanal. Chem. 2013, 405, 5341–5351. [Google Scholar] [CrossRef] [PubMed]
- Grishin, A.A.; Cuny, H.; Hung, A.; Clark, R.J.; Brust, A.; Akondi, K.; Alewood, P.F.; Craik, D.J.; Adams, D.J. Identifying Key Amino Acid Residues That Affect α-Conotoxin AuIB Inhibition of A3β4 Nicotinic Acetylcholine Receptors. J. Biol. Chem. 2013, 288, 34428–34442. [Google Scholar] [CrossRef] [Green Version]
- Li, L.; Liu, N.; Ding, R.; Wang, S.; Liu, Z.; Li, H.; Zheng, X.; Dai, Q. A Novel 4/6-Type Alpha-Conotoxin ViIA Selectively Inhibits NAchR A3β2 Subtype. Acta Biochim. Biophys. Sin. 2015, 47, 1023–1028. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- van Hout, M.; Valdes, A.; Christensen, S.B.; Tran, P.T.; Watkins, M.; Gajewiak, J.; Jensen, A.A.; Olivera, B.M.; McIntosh, J.M. α-Conotoxin VnIB from Conus Ventricosus Is a Potent and Selective Antagonist of A6β4* Nicotinic Acetylcholine Receptors. Neuropharmacology 2019, 157, 107691. [Google Scholar] [CrossRef] [PubMed]
- Wu, Y.; Zhangsun, D.; Zhu, X.; Kaas, Q.; Zhangsun, M.; Harvey, P.J.; Craik, D.J.; McIntosh, J.M.; Luo, S. α-Conotoxin [S9A]TxID Potently Discriminates between A3β4 and A6/A3β4 Nicotinic Acetylcholine Receptors. J. Med. Chem. 2017, 60, 5826–5833. [Google Scholar] [CrossRef] [PubMed]
- Loughnan, M.L.; Nicke, A.; Jones, A.; Adams, D.J.; Alewood, P.F.; Lewis, R.J. Chemical and Functional Identification and Characterization of Novel Sulfated α-Conotoxins from the Cone Snail Conus Anemone. J. Med. Chem. 2004, 47, 1234–1241. [Google Scholar] [CrossRef]
- Whiteaker, P.; Christensen, S.; Yoshikami, D.; Dowell, C.; Watkins, M.; Gulyas, J.; Rivier, J.; Olivera, B.M.; McIntosh, J.M. Discovery, Synthesis, and Structure Activity of a Highly Selective A7 Nicotinic Acetylcholine Receptor Antagonist. Biochemistry 2007, 46, 6628–6638. [Google Scholar] [CrossRef]
- Ning, J.; Ren, J.; Xiong, Y.; Wu, Y.; Zhangsun, M.; Zhangsun, D.; Zhu, X.; Luo, S. Identification of Crucial Residues in α-Conotoxin EI Inhibiting Muscle Nicotinic Acetylcholine Receptor. Toxins 2019, 11, 603. [Google Scholar] [CrossRef] [Green Version]
- Lin, B.; Xu, M.; Zhu, X.; Wu, Y.; Liu, X.; Zhangsun, D.; Hu, Y.; Xiang, S.-H.; Kasheverov, I.E.; Tsetlin, V.I.; et al. From Crystal Structure of α-Conotoxin GIC in Complex with Ac-AChBP to Molecular Determinants of Its High Selectivity for A3β2 NAChR. Sci. Rep. 2016, 6, 22349. [Google Scholar] [CrossRef] [Green Version]
- Banerjee, J.; Yongye, A.B.; Chang, Y.-P.; Gyanda, R.; Medina-Franco, J.L.; Armishaw, C.J. Design and Synthesis of α-Conotoxin GID Analogues as Selective A4β2 Nicotinic Acetylcholine Receptor Antagonists. Biopolymers 2014, 102, 78–87. [Google Scholar] [CrossRef]
- Lebbe, E.K.M.; Peigneur, S.; Maiti, M.; Devi, P.; Ravichandran, S.; Lescrinier, E.; Ulens, C.; Waelkens, E.; D’Souza, L.; Herdewijn, P.; et al. Structure-Function Elucidation of a New α-Conotoxin, Lo1a, from Conus Longurionis. J. Biol. Chem. 2014, 289, 9573–9583. [Google Scholar] [CrossRef] [Green Version]
- Inserra, M.C.; Kompella, S.N.; Vetter, I.; Brust, A.; Daly, N.L.; Cuny, H.; Craik, D.J.; Alewood, P.F.; Adams, D.J.; Lewis, R.J. Isolation and Characterization of α-Conotoxin LsIA with Potent Activity at Nicotinic Acetylcholine Receptors. Biochem. Pharmacol. 2013, 86, 791–799. [Google Scholar] [CrossRef] [PubMed]
- Chen, J.; Liang, L.; Ning, H.; Cai, F.; Liu, Z.; Zhang, L.; Zhou, L.; Dai, Q. Cloning, Synthesis and Functional Characterization of a Novel α-Conotoxin Lt1.3. Mar. Drugs 2018, 16, 112. [Google Scholar] [CrossRef] [Green Version]
- Luo, S.; Zhangsun, D.; Schroeder, C.I.; Zhu, X.; Hu, Y.; Wu, Y.; Weltzin, M.M.; Eberhard, S.; Kaas, Q.; Craik, D.J.; et al. A Novel A4/7-Conotoxin LvIA from Conus Lividus That Selectively Blocks A3β2 vs. A6/A3β2β3 Nicotinic Acetylcholine Receptors. FASEB J. 2014, 28, 1842–1853. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, M.; Zhu, X.; Yu, J.; Yu, J.; Luo, S.; Wang, X. The Crystal Structure of Ac-AChBP in Complex with α-Conotoxin LvIA Reveals the Mechanism of Its Selectivity towards Different NAChR Subtypes. Protein Cell 2017, 8, 675–685. [Google Scholar] [CrossRef] [PubMed]
- Everhart, D.; Cartier, G.E.; Malhotra, A.; Gomes, A.V.; McIntosh, J.M.; Luetje, C.W. Determinants of Potency on Alpha-Conotoxin MII, a Peptide Antagonist of Neuronal Nicotinic Receptors. Biochemistry 2004, 43, 2732–2737. [Google Scholar] [CrossRef]
- McIntosh, J.M.; Azam, L.; Staheli, S.; Dowell, C.; Lindstrom, J.M.; Kuryatov, A.; Garrett, J.E.; Marks, M.J.; Whiteaker, P. Analogs of Alpha-Conotoxin MII Are Selective for Alpha6-Containing Nicotinic Acetylcholine Receptors. Mol. Pharmacol. 2004, 65, 944–952. [Google Scholar] [CrossRef] [PubMed]
- Wang, S.; Zhao, C.; Liu, Z.; Wang, X.; Liu, N.; Du, W.; Dai, Q. Structural and Functional Characterization of a Novel α-Conotoxin Mr1.7 from Conus Marmoreus Targeting Neuronal NAChR A3β2, A9α10 and A6/A3β2β3 Subtypes. Mar. Drugs 2015, 13, 3259–3275. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hone, A.J.; Ruiz, M.; Scadden, M.; Christensen, S.; Gajewiak, J.; Azam, L.; McIntosh, J.M. Positional Scanning Mutagenesis of α-Conotoxin PeIA Identifies Critical Residues That Confer Potency and Selectivity for A6/A3β2β3 and A3β2 Nicotinic Acetylcholine Receptors. J. Biol. Chem. 2013, 288, 25428–25439. [Google Scholar] [CrossRef] [Green Version]
- Hone, A.J.; Fisher, F.; Christensen, S.; Gajewiak, J.; Larkin, D.; Whiteaker, P.; McIntosh, J.M. PeIA-5466: A Novel Peptide Antagonist Containing Non-Natural Amino Acids That Selectively Targets A3β2 Nicotinic Acetylcholine Receptors. J. Med. Chem. 2019, 62, 6262–6275. [Google Scholar] [CrossRef]
- Hone, A.J.; Scadden, M.; Gajewiak, J.; Christensen, S.; Lindstrom, J.; McIntosh, J.M. α-Conotoxin PeIA[S9H,V10A,E14N] Potently and Selectively Blocks A6β2β3 versus A6β4 Nicotinic Acetylcholine Receptors. Mol. Pharmacol. 2012, 82, 972–982. [Google Scholar] [CrossRef] [Green Version]
- Luo, S.; Nguyen, T.A.; Cartier, G.E.; Olivera, B.M.; Yoshikami, D.; McIntosh, J.M. Single-Residue Alteration in α-Conotoxin PnIA Switches Its NAChR Subtype Selectivity. Biochemistry 1999, 38, 14542–14548. [Google Scholar] [CrossRef] [PubMed]
- Hogg, R.C.; Hopping, G.; Alewood, P.F.; Adams, D.J.; Bertrand, D. Alpha-Conotoxins PnIA and [A10L]PnIA Stabilize Different States of the Alpha7-L247T Nicotinic Acetylcholine Receptor. J. Biol. Chem. 2003, 278, 26908–26914. [Google Scholar] [CrossRef] [Green Version]
- Kompella, S.N.; Hung, A.; Clark, R.J.; Marí, F.; Adams, D.J. Alanine Scan of α-Conotoxin RegIIA Reveals a Selective A3β4 Nicotinic Acetylcholine Receptor Antagonist. J. Biol. Chem. 2015, 290, 1039–1048. [Google Scholar] [CrossRef] [Green Version]
- Luo, S.; Zhangsun, D.; Zhu, X.; Wu, Y.; Hu, Y.; Christensen, S.; Harvey, P.J.; Akcan, M.; Craik, D.J.; McIntosh, J.M. Characterization of a Novel α-Conotoxin TxID from Conus Textile That Potently Blocks Rat A3β4 Nicotinic Acetylcholine Receptors. J. Med. Chem. 2013, 56, 9655–9663. [Google Scholar] [CrossRef] [Green Version]
- Jin, A.-H.; Vetter, I.; Dutertre, S.; Abraham, N.; Emidio, N.B.; Inserra, M.; Murali, S.S.; Christie, M.J.; Alewood, P.F.; Lewis, R.J. MrIC, a Novel α-Conotoxin Agonist in the Presence of PNU at Endogenous A7 Nicotinic Acetylcholine Receptors. Biochemistry 2014, 53, 1–3. [Google Scholar] [CrossRef]
- Halai, R.; Clark, R.J.; Nevin, S.T.; Jensen, J.E.; Adams, D.J.; Craik, D.J. Scanning Mutagenesis of Alpha-Conotoxin Vc1.1 Reveals Residues Crucial for Activity at the Alpha9alpha10 Nicotinic Acetylcholine Receptor. J. Biol. Chem. 2009, 284, 20275–20284. [Google Scholar] [CrossRef] [Green Version]
- Dutton, J.L.; Craik, D.J. Alpha-Conotoxins: Nicotinic Acetylcholine Receptor Antagonists as Pharmacological Tools and Potential Drug Leads. Curr. Med. Chem. 2001, 8, 327–344. [Google Scholar] [CrossRef]
- Halai, R.; Craik, D.J. Conotoxins: Natural Product Drug Leads. Nat. Prod. Rep. 2009, 26, 526–536. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; Tae, H.-S.; Chu, Y.; Jiang, T.; Adams, D.J.; Yu, R. Medicinal Chemistry, Pharmacology, and Therapeutic Potential of α-Conotoxins Antagonizing the A9α10 Nicotinic Acetylcholine Receptor. Pharmacol. Ther. 2020, 222, 107792. [Google Scholar] [CrossRef]
- Di Cesare Mannelli, L.; Cinci, L.; Micheli, L.; Zanardelli, M.; Pacini, A.; McIntosh, J.M.; Ghelardini, C. α-Conotoxin RgIA Protects against the Development of Nerve Injury-Induced Chronic Pain and Prevents Both Neuronal and Glial Derangement. Pain 2014, 155, 1986–1995. [Google Scholar] [CrossRef] [Green Version]
- Hone, A.J.; Servent, D.; McIntosh, J.M. A9-Containing Nicotinic Acetylcholine Receptors and the Modulation of Pain. Br. J. Pharmacol. 2018, 175, 1915–1927. [Google Scholar] [CrossRef] [Green Version]
- Mohammadi, S.; Christie, M.J. A9-Nicotinic Acetylcholine Receptors Contribute to the Maintenance of Chronic Mechanical Hyperalgesia, but Not Thermal or Mechanical Allodynia. Mol. Pain 2014, 10, 1744–8069. [Google Scholar] [CrossRef] [Green Version]
- Mohammadi, S.A.; Christie, M.J. Conotoxin Interactions with A9α10-NAChRs: Is the A9α10-Nicotinic Acetylcholine Receptor an Important Therapeutic Target for Pain Management? Toxins 2015, 7, 3916–3932. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vincler, M.; McIntosh, J.M. Targeting the A9α10 Nicotinic Acetylcholine Receptor to Treat Severe Pain. Expert Opin. Ther. Targets 2007, 11, 891–897. [Google Scholar] [CrossRef] [PubMed]
- Satkunanathan, N.; Livett, B.; Gayler, K.; Sandall, D.; Down, J.; Khalil, Z. Alpha-Conotoxin Vc1.1 Alleviates Neuropathic Pain and Accelerates Functional Recovery of Injured Neurones. Brain Res. 2005, 1059, 149–158. [Google Scholar] [CrossRef]
- Romero, H.K.; Christensen, S.B.; Di Cesare Mannelli, L.; Gajewiak, J.; Ramachandra, R.; Elmslie, K.S.; Vetter, D.E.; Ghelardini, C.; Iadonato, S.P.; Mercado, J.L.; et al. Inhibition of A9α10 Nicotinic Acetylcholine Receptors Prevents Chemotherapy-Induced Neuropathic Pain. Proc. Natl. Acad. Sci. USA 2017, 114, E1825–E1832. [Google Scholar] [CrossRef] [Green Version]
- Christensen, S.B.; Hone, A.J.; Roux, I.; Kniazeff, J.; Pin, J.-P.; Upert, G.; Servent, D.; Glowatzki, E.; McIntosh, J.M. RgIA4 Potently Blocks Mouse A9α10 NAChRs and Provides Long Lasting Protection against Oxaliplatin-Induced Cold Allodynia. Front. Cell. Neurosci. 2017, 11, 219. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- AlSharari, S.D.; Toma, W.; Mahmood, H.M.; Michael McIntosh, J.; Imad Damaj, M. The A9α10 Nicotinic Acetylcholine Receptors Antagonist α-Conotoxin RgIA Reverses Colitis Signs in Murine Dextran Sodium Sulfate Model. Eur. J. Pharmacol. 2020, 883, 173320. [Google Scholar] [CrossRef]
- Qian, J.; Liu, Y.-Q.; Sun, Z.-H.; Zhangsun, D.-T.; Luo, S.-L. Identification of Nicotinic Acetylcholine Receptor Subunits in Different Lung Cancer Cell Lines and the Inhibitory Effect of Alpha-Conotoxin TxID on Lung Cancer Cell Growth. Eur. J. Pharmacol. 2019, 865, 172674. [Google Scholar] [CrossRef] [PubMed]
- Bertrand, D.; Terry, A.V.J. The Wonderland of Neuronal Nicotinic Acetylcholine Receptors. Biochem. Pharmacol. 2018, 151, 214–225. [Google Scholar] [CrossRef]
- Ellison, M.; Gao, F.; Wang, H.-L.; Sine, S.M.; McIntosh, J.M.; Olivera, B.M. α-Conotoxins ImI and ImII Target Distinct Regions of the Human A7 Nicotinic Acetylcholine Receptor and Distinguish Human Nicotinic Receptor Subtypes. Biochemistry 2004, 43, 16019–16026. [Google Scholar] [CrossRef] [PubMed]
- Ellison, M.; Haberlandt, C.; Gomez-Casati, M.E.; Watkins, M.; Elgoyhen, A.B.; McIntosh, J.M.; Olivera, B.M. α-RgIA: A Novel Conotoxin That Specifically and Potently Blocks the A9α10 NAChR. Biochemistry 2006, 45, 1511–1517. [Google Scholar] [CrossRef]
- López-Vera, E.; Jacobsen, R.B.; Ellison, M.; Olivera, B.M.; Teichert, R.W. A Novel Alpha Conotoxin (Alpha-PIB) Isolated from C. Purpurascens Is Selective for Skeletal Muscle Nicotinic Acetylcholine Receptors. Toxicon 2007, 49, 1193–1199. [Google Scholar] [CrossRef]
- Luo, S.; Kulak, J.M.; Cartier, G.E.; Jacobsen, R.B.; Yoshikami, D.; Olivera, B.M.; McIntosh, J.M. Alpha-Conotoxin AuIB Selectively Blocks Alpha3 Beta4 Nicotinic Acetylcholine Receptors and Nicotine-Evoked Norepinephrine Release. J. Neurosci. 1998, 18, 8571–8579. [Google Scholar] [CrossRef] [Green Version]
- Nicke, A.; Samochocki, M.; Loughnan, M.L.; Bansal, P.S.; Maelicke, A.; Lewis, R.J. α-Conotoxins EpI and AuIB Switch Subtype Selectivity and Activity in Native versus Recombinant Nicotinic Acetylcholine Receptors. FEBS Lett. 2003, 554, 219–223. [Google Scholar] [CrossRef] [Green Version]
- Martinez, J.S.; Olivera, B.M.; Gray, W.R.; Craig, A.G.; Groebe, D.R.; Abramson, S.N.; McIntosh, J.M. Alpha.-Conotoxin EI, A New Nicotinic Acetylcholine Receptor Antagonist with Novel Selectivity. Biochemistry 1995, 34, 14519–14526. [Google Scholar] [CrossRef] [PubMed]
- McIntosh, J.M.; Dowell, C.; Watkins, M.; Garrett, J.E.; Yoshikami, D.; Olivera, B.M. α-Conotoxin GIC from Conus Geographus, a Novel Peptide Antagonist of Nicotinic Acetylcholine Receptors. J. Biol. Chem. 2002, 277, 33610–33615. [Google Scholar] [CrossRef] [Green Version]
- Nicke, A.; Loughnan, M.L.; Millard, E.L.; Alewood, P.F.; Adams, D.J.; Daly, N.L.; Craik, D.J.; Lewis, R.J. Isolation, Structure, and Activity of GID, a Novel Alpha 4/7-Conotoxin with an Extended N-Terminal Sequence. J. Biol. Chem. 2003, 278, 3137–3144. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Millard, E.L.; Nevin, S.T.; Loughnan, M.L.; Nicke, A.; Clark, R.J.; Alewood, P.F.; Lewis, R.J.; Adams, D.J.; Craik, D.J.; Daly, N.L. Inhibition of Neuronal Nicotinic Acetylcholine Receptor Subtypes by Alpha-Conotoxin GID and Analogues. J. Biol. Chem. 2009, 284, 4944–4951. [Google Scholar] [CrossRef] [Green Version]
- Luo, S.; Akondi, K.B.; Zhangsun, D.; Wu, Y.; Zhu, X.; Hu, Y.; Christensen, S.; Dowell, C.; Daly, N.L.; Craik, D.J.; et al. Atypical α-Conotoxin LtIA from Conus Litteratus Targets a Novel Microsite of the A3β2 Nicotinic Receptor. J. Biol. Chem. 2010, 285, 12355–12366. [Google Scholar] [CrossRef] [Green Version]
- Cartier, G.E.; Yoshikami, D.; Gray, W.R.; Luo, S.; Olivera, B.M.; McIntosh, J.M. A New α-Conotoxin Which Targets A3β2 Nicotinic Acetylcholine Receptors. J. Biol. Chem. 1996, 271, 7522–7528. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- McIntosh, J.M.; Plazas, P.V.; Watkins, M.; Gomez-Casati, M.E.; Olivera, B.M.; Elgoyhen, A.B. A Novel Alpha-Conotoxin, PeIA, Cloned from Conus Pergrandis, Discriminates between Rat Alpha9alpha10 and Alpha7 Nicotinic Cholinergic Receptors. J. Biol. Chem. 2005, 280, 30107–30112. [Google Scholar] [CrossRef] [Green Version]
- Franco, A.; Kompella, S.N.; Akondi, K.B.; Melaun, C.; Daly, N.L.; Luetje, C.W.; Alewood, P.F.; Craik, D.J.; Adams, D.J.; Marí, F. RegIIA: An A4/7-Conotoxin from the Venom of Conus Regius That Potently Blocks A3β4 NAChRs. Biochem. Pharmacol. 2012, 83, 419–426. [Google Scholar] [CrossRef] [PubMed]
- Clark, R.J.; Fischer, H.; Nevin, S.T.; Adams, D.J.; Craik, D.J. The Synthesis, Structural Characterization, and Receptor Specificity of the Alpha-Conotoxin Vc1.1. J. Biol. Chem. 2006, 281, 23254–23263. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kessler, P.; Marchot, P.; Silva, M.; Servent, D. The Three-Finger Toxin Fold: A Multifunctional Structural Scaffold Able to Modulate Cholinergic Functions. J. Neurochem. 2017, 142, 7–18. [Google Scholar] [CrossRef]
- Tsetlin, V.I.; Kasheverov, I.E.; Utkin, Y.N. Three-Finger Proteins from Snakes and Humans Acting on Nicotinic Receptors: Old and New. J. Neurochem. 2020. [Google Scholar] [CrossRef]
- Nirthanan, S.; Gopalakrishnakone, P.; Gwee, M.C.E.; Khoo, H.E.; Kini, R.M. Non-Conventional Toxins from Elapid Venoms. Toxicon 2003, 41, 397–407. [Google Scholar] [CrossRef]
- Utkin, Y.N.; Kukhtina, V.V.; Kryukova, E.V.; Chiodini, F.; Bertrand, D.; Methfessel, C.; Tsetlin, V.I. “Weak Toxin” from Naja Kaouthia Is a Nontoxic Antagonist of A7 and Muscle-Type Nicotinic Acetylcholine Receptors. J. Biol. Chem. 2001, 276, 15810–15815. [Google Scholar] [CrossRef] [Green Version]
- Nirthanan, S.; Charpantier, E.; Gopalakrishnakone, P.; Gwee, M.C.E.; Khoo, H.-E.; Cheah, L.-S.; Bertrand, D.; Kini, R.M. Candoxin, a Novel Toxin from Bungarus Candidus, Is a Reversible Antagonist of Muscle (Aβγδ) but a Poorly Reversible Antagonist of Neuronal A7 Nicotinic Acetylcholine Receptors. J. Biol. Chem. 2002, 277, 17811–17820. [Google Scholar] [CrossRef] [Green Version]
- Osipov, A.V.; Kasheverov, I.E.; Makarova, Y.V.; Starkov, V.G.; Vorontsova, O.V.; Ziganshin, R.K.; Andreeva, T.V.; Serebryakova, M.V.; Benoit, A.; Hogg, R.C.; et al. Naturally Occurring Disulfide-Bound Dimers of Three-Fingered Toxins. J. Biol. Chem. 2008, 283, 14571–14580. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Osipov, A.V.; Rucktooa, P.; Kasheverov, I.E.; Filkin, S.Y.; Starkov, V.G.; Andreeva, T.V.; Sixma, T.K.; Bertrand, D.; Utkin, Y.N.; Tsetlin, V.I. Dimeric α-Cobratoxin X-ray structure: Localization of intermolecular disulfides and possible mode of binding to nicotinic acetylcholine receptors. J. Biol. Chem. 2012, 287, 6725–6734. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Foo, C.S.; Jobichen, C.; Hassan-Puttaswamy, V.; Dekan, Z.; Tae, H.-S.; Bertrand, D.; Adams, D.J.; Alewood, P.F.; Sivaraman, J.; Nirthanan, S.; et al. Fulditoxin, Representing a New Class of Dimeric Snake Toxins, Defines Novel Pharmacology at Nicotinic ACh Receptors. Br. J. Pharmacol. 2020, 177, 1822–1840. [Google Scholar] [CrossRef] [PubMed]
- Pawlak, J.; Mackessy, S.P.; Sixberry, N.M.; Stura, E.A.; Le Du, M.H.; Ménez, R.; Foo, C.S.; Ménez, A.; Nirthanan, S.; Kini, R.M. Irditoxin, a Novel Covalently Linked Heterodimeric Three-Finger Toxin with High Taxon-Specific Neurotoxicity. FASEB J. 2009, 23, 534–545. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nirthanan, S. Snake Three-Finger α-Neurotoxins and Nicotinic Acetylcholine Receptors: Molecules, Mechanisms and Medicine. Biochem. Pharmacol. 2020, 181, 114168. [Google Scholar] [CrossRef] [PubMed]
- Chang, C.C. Looking Back on the Discovery of α-Bungarotoxin. J. Biomed. Sci. 1999, 6, 368–375. [Google Scholar] [CrossRef]
- Changeux, J.P.; Kasai, M.; Lee, C.Y. Use of a Snake Venom Toxin to Characterize the Cholinergic Receptor Protein. Proc. Natl. Acad. Sci. USA 1970, 67, 1241–1247. [Google Scholar] [CrossRef] [Green Version]
- Wang, G.K.; Schmidt, J. Primary Structure and Binding Properties of Iodinated Derivatives of Alpha-Bungarotoxin. J. Biol. Chem. 1980, 255, 11156–11162. [Google Scholar] [CrossRef]
- Servent, D.; Mourier, G.; Antil, S.; Ménez, A. How Do Snake Curaremimetic Toxins Discriminate between Nicotinic Acetylcholine Receptor Subtypes. Toxicol. Lett. 1998, 102–103, 199–203. [Google Scholar] [CrossRef]
- Moise, L.; Piserchio, A.; Basus, V.J.; Hawrot, E. NMR Structural Analysis of α-Bungarotoxin and Its Complex with the Principal α-Neurotoxin-Binding Sequence on the A7 Subunit of a Neuronal Nicotinic Acetylcholine Receptor. J. Biol. Chem. 2002, 277, 12406–12417. [Google Scholar] [CrossRef] [Green Version]
- Dellisanti, C.D.; Yao, Y.; Stroud, J.C.; Wang, Z.-Z.; Chen, L. Crystal Structure of the Extracellular Domain of NAChR A1 Bound to α-Bungarotoxin at 1.94 Å Resolution. Nat. Neurosci. 2007, 10, 953–962. [Google Scholar] [CrossRef]
- Huang, S.; Li, S.-X.; Bren, N.; Cheng, K.; Gomoto, R.; Chen, L.; Sine, S.M. Complex between α-Bungarotoxin and an A7 Nicotinic Receptor Ligand-Binding Domain Chimaera. Biochem. J. 2013, 454, 303–310. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zouridakis, M.; Giastas, P.; Zarkadas, E.; Chroni-Tzartou, D.; Bregestovski, P.; Tzartos, S.J. Crystal Structures of Free and Antagonist-Bound States of Human A9 Nicotinic Receptor Extracellular Domain. Nat. Struct. Mol. Biol. 2014, 21, 976–980. [Google Scholar] [CrossRef]
- Rahman, M.M.; Teng, J.; Worrell, B.T.; Noviello, C.M.; Lee, M.; Karlin, A.; Stowell, M.H.B.; Hibbs, R.E. Structure of the Native Muscle-Type Nicotinic Receptor and Inhibition by Snake Venom Toxins. Neuron 2020, 106, 952–962.e5. [Google Scholar] [CrossRef]
- Antil-Delbeke, S.; Gaillard, C.; Tamiya, T.; Corringer, P.-J.; Changeux, J.-P.; Servent, D.; Ménez, A. Molecular Determinants by Which a Long Chain Toxin from Snake Venom Interacts with the Neuronal A7-Nicotinic Acetylcholine Receptor. J. Biol. Chem. 2000, 275, 29594–29601. [Google Scholar] [CrossRef] [Green Version]
- Fruchart-Gaillard, C.; Gilquin, B.; Antil-Delbeke, S.; Le Novère, N.; Tamiya, T.; Corringer, P.-J.; Changeux, J.-P.; Ménez, A.; Servent, D. Experimentally Based Model of a Complex between a Snake Toxin and the A7 Nicotinic Receptor. Proc. Natl. Acad. Sci. USA 2002, 99, 3216. [Google Scholar] [CrossRef] [Green Version]
- Bourne, Y.; Talley, T.T.; Hansen, S.B.; Taylor, P.; Marchot, P. Crystal Structure of a Cbtx–AChBP Complex Reveals Essential Interactions between Snake α-Neurotoxins and Nicotinic Receptors. EMBO J. 2005, 24, 1512–1522. [Google Scholar] [CrossRef] [Green Version]
- Utkin, Y.N.; Kuch, U.; Kasheverov, I.E.; Lebedev, D.S.; Cederlund, E.; Molles, B.E.; Polyak, I.; Ivanov, I.A.; Prokopev, N.A.; Ziganshin, R.H.; et al. Novel Long-Chain Neurotoxins from Bungarus Candidus Distinguish the Two Binding Sites in Muscle-Type Nicotinic Acetylcholine Receptors. Biochem. J. 2019, 476, 1285–1302. [Google Scholar] [CrossRef]
- Chandna, R.; Tae, H.-S.; Seymour, V.A.L.; Chathrath, S.; Adams, D.J.; Kini, R.M. Drysdalin, an Antagonist of Nicotinic Acetylcholine Receptors Highlights the Importance of Functional Rather than Structural Conservation of Amino Acid Residues. FASEB BioAdv. 2019, 1, 115–131. [Google Scholar] [CrossRef] [Green Version]
- Servent, D.; Winckler-Dietrich, V.; Hu, H.-Y.; Kessler, P.; Drevet, P.; Bertrand, D.; Ménez, A. Only Snake Curaremimetic Toxins with a Fifth Disulfide Bond Have High Affinity for the Neuronal A7 Nicotinic Receptor. J. Biol. Chem. 1997, 272, 24279–24286. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Trémeau, O.; Lemaire, C.; Drevet, P.; Pinkasfeld, S.; Ducancel, F.; Boulain, J.-C.; Ménez, A. Genetic Engineering of Snake Toxins: The functional site of Erabutoxin a, as delineated by site-directed mutagenesis, includes variant residues. J. Biol. Chem. 1995, 270, 9362–9369. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Teixeira-Clerc, F.; Ménez, A.; Kessler, P. How Do Short Neurotoxins Bind to a Muscular-Type Nicotinic Acetylcholine Receptor? J. Biol. Chem. 2002, 277, 25741–25747. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ackermann, E.J.; Taylor, P. Nonidentity of the α-Neurotoxin Binding Sites on the Nicotinic Acetylcholine Receptor Revealed by Modification in α-Neurotoxin and Receptor Structures. Biochemistry 1997, 36, 12836–12844. [Google Scholar] [CrossRef] [PubMed]
- Osaka, H.; Malany, S.; Kanter, J.R.; Sine, S.M.; Taylor, P. Subunit Interface Selectivity of the Alpha-Neurotoxins for the Nicotinic Acetylcholine Receptor. J. Biol. Chem. 1999, 274, 9581–9586. [Google Scholar] [CrossRef] [Green Version]
- Roy, A.; Zhou, X.; Chong, M.Z.; D’hoedt, D.; Foo, C.S.; Rajagopalan, N.; Nirthanan, S.; Bertrand, D.; Sivaraman, J.; Kini, R.M. Structural and Functional Characterization of a Novel Homodimeric Three-Finger Neurotoxin from the Venom of Ophiophagus Hannah (King Cobra). J. Biol. Chem. 2010, 285, 8302–8315. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Betzel, C.; Lange, G.; Pal, G.P.; Wilson, K.S.; Maelicke, A.; Saenger, W. The Refined Crystal Structure of Alpha-Cobratoxin from Naja Naja Siamensis at 2.4-A Resolution. J. Biol. Chem. 1991, 266, 21530–21536. [Google Scholar] [CrossRef]
- Chatrath, S.T.; Chapeaurouge, A.; Lin, Q.; Lim, T.K.; Dunstan, N.; Mirtschin, P.; Kumar, P.P.; Kini, R.M. Identification of Novel Proteins from the Venom of a Cryptic Snake Drysdalia Coronoides by a Combined Transcriptomics and Proteomics Approach. J. Proteome Res. 2011, 10, 739–750. [Google Scholar] [CrossRef] [PubMed]
- Pillet, L.; Trémeau, O.; Ducancel, F.; Drevet, P.; Zinn-Justin, S.; Pinkasfeld, S.; Boulain, J.C.; Ménez, A. Genetic Engineering of Snake Toxins. Role of Invariant Residues in the Structural and Functional Properties of a Curaremimetic Toxin, as Probed by Site-Directed Mutagenesis. J. Biol. Chem. 1993, 268, 909–916. [Google Scholar] [CrossRef]
- Dewan, J.C.; Grant, G.A.; Sacchettini, J.C. Crystal Structure of Kappa-Bungarotoxin at 2.3-A Resolution. Biochemistry 1994, 33, 13147–13154. [Google Scholar] [CrossRef]
- Chiappinelli, V.A.; Weaver, W.R.; McLane, K.E.; Conti-Fine, B.M.; Fiordalisi, J.J.; Grant, G.A. Binding of Native κ-Neurotoxins and Site-Directed Mutants to Nicotinic Acetylcholine Receptors. Toxicon 1996, 34, 1243–1256. [Google Scholar] [CrossRef]
- Mordvintsev, D.Y.; Polyak, Y.L.; Rodionov, D.I.; Jakubik, J.; Dolezal, V.; Karlsson, E.; Tsetlin, V.I.; Utkin, Y.N. Weak Toxin WTX from Naja Kaouthia Cobra Venom Interacts with Both Nicotinic and Muscarinic Acetylcholine Receptors. FEBS J. 2009, 276, 5065–5075. [Google Scholar] [CrossRef]
- Lyukmanova, E.N.; Shulepko, M.A.; Shenkarev, Z.O.; Kasheverov, I.E.; Chugunov, A.O.; Kulbatskii, D.S.; Myshkin, M.Y.; Utkin, Y.N.; Efremov, R.G.; Tsetlin, V.I.; et al. Central Loop of Non-Conventional Toxin WTX from Naja Kaouthia Is Important for Interaction with Nicotinic Acetylcholine Receptors. Toxicon 2016, 119, 274–279. [Google Scholar] [CrossRef] [PubMed]
- Pawlak, J.; Mackessy, S.P.; Fry, B.G.; Bhatia, M.; Mourier, G.; Fruchart-Gaillard, C.; Servent, D.; Ménez, R.; Stura, E.; Ménez, A.; et al. Denmotoxin, a Three-Finger Toxin from the Colubrid Snake Boiga Dendrophila (Mangrove Catsnake) with Bird-Specific Activity. J. Biol. Chem. 2006, 281, 29030–29041. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, H.S.; Tamiya, N. Amino Acid Sequences of Two Novel Long-Chain Neurotoxins from the Venom of the Sea Snake Laticauda Colubrina. Biochem. J. 1982, 207, 215–223. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chang, L.-S.; Liou, J.-C.; Lin, S.-R.; Huang, H.-B. Purification and Characterization of a Neurotoxin from the Venom of Ophiophagus Hannah (King Cobra). Biochem. Biophys. Res. Commun. 2002, 294, 574–578. [Google Scholar] [CrossRef]
- Hassan-Puttaswamy, V.; Adams, D.J.; Kini, R.M. A Distinct Functional Site in Ω-Neurotoxins: Novel Antagonists of Nicotinic Acetylcholine Receptors from Snake Venom. ACS Chem. Biol. 2015, 10, 2805–2815. [Google Scholar] [CrossRef]
- Molles, B.E.; Rezai, P.; Kline, E.F.; McArdle, J.J.; Sine, S.M.; Taylor, P. Identification of Residues at the α and ε Subunit Interfaces Mediating Species Selectivity of Waglerin-1 for Nicotinic Acetylcholine Receptors. J. Biol. Chem. 2002, 277, 5433–5440. [Google Scholar] [CrossRef] [Green Version]
- Ye, J.-H.; McArdle, J.J. Waglerin-1 Modulates γ-Aminobutyric Acid Activated Current of Murine Hypothalamic Neurons. J. Pharmacol. Exp. Ther. 1997, 282, 74. [Google Scholar]
- Sellin, L.C.; Mattila, K.; Annila, A.; Schmidt, J.J.; McArdle, J.J.; Hyvönen, M.; Rantala, T.T.; Kivistö, T. Conformational Analysis of a Toxic Peptide from Trimeresurus Wagleri Which Blocks the Nicotinic Acetylcholine Receptor. Biophys. J. 1996, 70, 3–13. [Google Scholar] [CrossRef] [Green Version]
- Lyukmanova, E.N.; Shenkarev, Z.O.; Shulepko, M.A.; Paramonov, A.S.; Chugunov, A.O.; Janickova, H.; Dolejsi, E.; Dolezal, V.; Utkin, Y.N.; Tsetlin, V.I.; et al. Structural Insight into Specificity of Interactions between Nonconventional Three-Finger Weak Toxin from Naja Kaouthia (WTX) and Muscarinic Acetylcholine Receptors. J. Biol. Chem. 2015, 290, 23616–23630. [Google Scholar] [CrossRef] [Green Version]
- McArdle, J.J.; Lentz, T.L.; Witzemann, V.; Schwarz, H.; Weinstein, S.A.; Schmidt, J.J. Waglerin-1 Selectively Blocks the Epsilon Form of the Muscle Nicotinic Acetylcholine Receptor. J. Pharmacol. Exp. Ther. 1999, 289, 543. [Google Scholar]
- Liang, S.; Zhang, D.; Pan, X.; Chen, Q.; Zhou, P. Properties and Amino Acid Sequence of Huwentoxin-I, a Neurotoxin Purified from the Venom of the Chinese Bird Spider Selenocosmia Huwena. Toxicon 1993, 31, 969–978. [Google Scholar] [CrossRef]
- Zhou, P.; Xie, X.; Li, M.; Yang, D.; Xie, Z.-P.; Zong, X.; Liang, S. Blockade of Neuromuscular Transmission by Huwentoxin-I, Purified from the Venom of the Chinese Bird Spider Selenocosmia Huwena. Toxicon 1997, 35, 39–45. [Google Scholar] [CrossRef]
- Liang, S.-P.; Chen, X.-D.; Shu, Q.; Zhang, Y.; Peng, K. The Presynaptic Activity of Huwentoxin-I, a Neurotoxin from the Venom of the Chinese Bird Spider Selenocosmia Huwena. Toxicon 2000, 38, 1237–1246. [Google Scholar] [CrossRef]
- Peng, K.; Chen, X.D.; Liang, S.P. The Effect of Huwentoxin-I on Ca(2+) Channels in Differentiated NG108-15 Cells, a Patch-Clamp Study. Toxicon 2001, 39, 491–498. [Google Scholar] [CrossRef]
- Wang, M.; Guan, X.; Liang, S. The Cross Channel Activities of Spider Neurotoxin Huwentoxin-I on Rat Dorsal Root Ganglion Neurons. Biochem. Biophys. Res. Commun. 2007, 357, 579–583. [Google Scholar] [CrossRef] [PubMed]
- Granja, R.; Fernández-Fernández, J.; Izaguirre, V.; González-García, C.; Ceña, V. ω-Agatoxin IVA Blocks Nicotinic Receptor Channels in Bovine Chromaffin Cells. FEBS Lett. 1995, 362, 15–18. [Google Scholar] [CrossRef] [Green Version]
- Wang, J.; Irnaten, M.; Mendelowitz, D. Agatoxin-IVA-Sensitive Calcium Channels Mediate the Presynaptic and Postsynaptic Nicotinic Activation of Cardiac Vagal Neurons. J. Neurophysiol. 2001, 85, 164–168. [Google Scholar] [CrossRef] [Green Version]
- Adams, M.E. Agatoxins: Ion Channel Specific Toxins from the American Funnel Web Spider, Agelenopsis Aperta. Toxicon 2004, 43, 509–525. [Google Scholar] [CrossRef]
- Windley, M.J.; Vetter, I.; Lewis, R.J.; Nicholson, G.M. Lethal Effects of an Insecticidal Spider Venom Peptide Involve Positive Allosteric Modulation of Insect Nicotinic Acetylcholine Receptors. Neuropharmacology 2017, 127, 224–242. [Google Scholar] [CrossRef] [Green Version]
- Bergeron, Z.L.; Bingham, J.-P. Scorpion Toxins Specific for Potassium (K+) Channels: A Historical Overview of Peptide Bioengineering. Toxins 2012, 4, 1082–1119. [Google Scholar] [CrossRef] [Green Version]
- Gurevitz, M.; Gordon, D.; Barzilai, M.G.; Kahn, R.; Cohen, L.; Moran, Y.; Zilberberg, N.; Froy, O.; Altman-Gueta, H.; Turkov, M.; et al. Molecular Description of Scorpion Toxin Interaction with Voltage-Gated Sodium Channels. In Scorpion Venoms; Gopalakrishnakone, P., Possani, L.D., Schwartz, E., Rodríguez de la Vega, R.C., Eds.; Springer: Dordrecht, The Netherlands, 2015; pp. 471–491. ISBN 978-94-007-6404-0. [Google Scholar]
- Quintero-Hernández, V.; Jiménez-Vargas, J.M.; Gurrola, G.B.; Valdivia, H.H.; Possani, L.D. Scorpion Venom Components That Affect Ion-Channels Function. Toxicon 2013, 76, 328–342. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kasheverov, I.E.; Oparin, P.B.; Zhmak, M.N.; Egorova, N.S.; Ivanov, I.A.; Gigolaev, A.M.; Nekrasova, O.V.; Serebryakova, M.V.; Kudryavtsev, D.S.; Prokopev, N.A.; et al. Scorpion Toxins Interact with Nicotinic Acetylcholine Receptors. FEBS Lett. 2019, 593, 2779–2789. [Google Scholar] [CrossRef] [PubMed]
- Mouhat, S.; Visan, V.; Ananthakrishnan, S.; Wulff, H.; Andreotti, N.; Grissmer, S.; Darbon, H.; De Waard, M.; Sabatier, J.-M. K+ Channel Types Targeted by Synthetic OSK1, a Toxin from Orthochirus Scrobiculosus Scorpion Venom. Biochem. J. 2004, 385, 95–104. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Toxin Same (UniProt) | Snake Species | Target (IC50 or Kd Values) | Ref. |
---|---|---|---|
α-bungarotoxin (P60615) | Multibanded krait Bungarus multicinctus (Elapidae) | Torpedo nAChRs (IC50 = 0.4 nM) hα7 (IC50 = 0.4 nM) α7-5HT3 chimera (IC50 = 0.95 nM) | [119] |
α-cobratoxin (P01391) | Indo-Chinese spitting cobra Naja naja siamensis (Elapidae) | Ac-AChBP (IC50 = 191 nM) Ls-AChBP (IC50 = 3.2 nM) α7 (IC50 = 0.3 nM) α7-5HT3 chimera (IC50 = 9 nM) | [119,125] |
αδ-bungarotoxin-1 | Blue krait Bungarus candidus (Elapidae) | T.californica nAChRs (IC50 = 11.4 nM) hα7 (IC50 = 1.18 nM) mα1β1δε (IC50 = 15.7 nM) mα1β1δγ (IC50 = 2.54 nM) (high affinity site α-δ 0.0212 nM on α1β1δε 0.115 nM on α1β1δγ; low affinity sites α-ε = 20.3 nM α-γ = 21.8 nM) | [117] |
Drysdalin (F8J2B3) | White-lipped snake Drysdalia coronoides (Elapidae) | rodent α1β1δε (IC50 = 16.9 nM) hα7 (IC50 = 10 nM) hα9α10 (IC50 = 11.3 nM) | [118,126] |
Erabutoxin -a (P60775) Erabutoxin-b (Q90VW1) | Chinese sea snake Laticauda semifasciata (Elapidae) | Torpedo nAChR (Kd = 0.07 nM) α7 (IC50 = 0.5 μ) α7-5HT3 chimera: Erabutoxin a (IC50 = 21 nM) Erabutoxin b (IC50 = 22 nM) | [120,121,127] |
NmmI | Mozambique spitting cobra Naja mossambica (Elapidae) | α1-γ and α1-δ interfaces (Kd = 100 pM) α1-ε interface (Kd = 100 nM) | [122,123] |
κ-Bungarotoxin homodimer (P01398) | Multibanded krait Bungarus multicinctus (Elapidae) | α3β2 (IC50 = 3 nM) α7 and α4β2-weak inhibition | [128,129] |
α-cobratoxin homodimer | Monocled cobra Naja kaouthia (Elapidae) | α1β1δγ of Torpedo (IC50 = 10 nM) α7 (IC50 = 0.2 μM) α3β2 (IC50 = 0.15 μM) | [100,101] |
Haditoxin (A8N286) | King cobra Ophiophagus hannah (Elapidae) | α7 (IC50 = 0.2 μM) α1β1δγ (IC50 = 0.5 μM) α3β2 (IC50 = 0.5 μM) α4β2 (IC50 = 2.6 μM) | [124] |
Fulditoxin | Eastern coral snake Micrurus fulvius fulvius (Elapidae) | rαβδε (IC50 = 2.6 μM) hα4β2 (IC50 = 1.8 µM) hα7 (IC50 = 7 µM) hα3β2 (IC50 = 12.6 µM) reversible blockade | [102] |
Irditoxin A and B (A0S864, A0S865) | Brown tree snake Boiga irregularis (Colubridae) | Species specific activity: avian α1β1δγ (IC50 = 10 nM) rodent α1β1δγ (IC50 > 10 µM) | [103] |
Candoxin (P81783) | Malayan krait Bungarus candidus (Elapidae) | rα1β1δγ nAChRs (IC50 = 10 nM), reversible block rα7 nAChRs (IC50 = 50 nM), irreversible block | [97,99] |
Weak toxin (WTX) (P82935) | Monocled cobra Naja kaouthia (Elapidae) | Torpedo nAChR (Kd = 90 nM) (native toxin) hα7 (IC50 = 14.8 μM) (recombinant) T.californica (IC50 = 3 μM) (recombinant) | [98,130,131] |
Denmotoxin (Q06ZW0) | Mangrove snake Boiga dendrophila (Colubridae) | Bird specific postsynaptic activity—irreversible inhibition at chick biventer neuromuscular preparation at 10 μg/mL (IC50 ~ 300 nM) | [132] |
Lc-a (P0C8R7) Lc-b (P0C8R8) | Yellow-lipped sea krait Laticauda colubrina (Elapidae) | Muscle nAChR LD50 = 0.12 μ/g following intramuscular injection in mice | [133] |
Neurotoxin Oh-9 (P83302) | King cobra Ophiophagus hannah (Elapidae) | IC50 on carbachol-induced chicken cervicis muscle contraction—88 nM; Rat adult muscle (IC50 = 3.1 μM) Rat fetal muscle (IC50 = 5.6 μM) | [134,135] |
Waglerin-1 (P24335) | Wagler’s palm viper Trimeresurus wagleri (Viperidae) | mα1β1δε (IC50 = 50 nM, end-plate potential inhibition); mα1β1δγ (IC50 = 36 μM); 2000-fold higher affinity to the α-ε (Kd = 9.8 nM) than to the α-δ (Kd = 20.2 μM) binding site interface of the mouse muscle receptor; hα1β1δε (Kd1 = 692 nM, Kd2 = 200 μM) rα1β1δε (Kd1 = 1.1 μM, Kd2 = 36 μM) | [136,137,138] |
Toxin Name/Spider Species/UniProt | Amino-Acid Sequence | Ref. |
---|---|---|
HWTX-I Selenocosmia huwena P56676 | ACKGVFDACTPGKNECCPNRVCSDKHKWCKWKL | [142] |
Ω-agatoxin IVA Agenelopsis aperta P30288 | KKKCIAKDYGRCKWGGTPCCRGRGCCSIMGTNCECPRLIMEGLGLA | [146] |
κ-HXTX-Hv1c Hadronyche versuta P82228 | AICTGADRPCAACCPCCPGTSCKAESNGVSYCRKDEP | [149] |
Toxin Name/ Species | Structure | IC50 | Ref. |
---|---|---|---|
OSK-1 (α-KTx family)/Orthochirus scrobiculosus | GVIINVKCKISRQCLEPCKKAGMRFGKCMNGKCHCTPK |
| [153,154] |
HelaTx1 (κ-KTx family)/Heterometrus laoticus | SCKKECSGSRRTKKCMOKCNREHGH |
| [153] |
Spinoxin/Heterometrus spinifer | IRCSGSRDCYSPCMKQTGCPNAKCINKSCKCYGC |
| [153] |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Bekbossynova, A.; Zharylgap, A.; Filchakova, O. Venom-Derived Neurotoxins Targeting Nicotinic Acetylcholine Receptors. Molecules 2021, 26, 3373. https://doi.org/10.3390/molecules26113373
Bekbossynova A, Zharylgap A, Filchakova O. Venom-Derived Neurotoxins Targeting Nicotinic Acetylcholine Receptors. Molecules. 2021; 26(11):3373. https://doi.org/10.3390/molecules26113373
Chicago/Turabian StyleBekbossynova, Ayaulym, Albina Zharylgap, and Olena Filchakova. 2021. "Venom-Derived Neurotoxins Targeting Nicotinic Acetylcholine Receptors" Molecules 26, no. 11: 3373. https://doi.org/10.3390/molecules26113373