Analysis of Conformational Differences of Copper and Alkali Metal Complexes of Insulin Using Trapped Ion Mobility-Mass Spectrometry Technique
Abstract
Molecular recognition, protein folding, and formation of supramolecular structures that occur at the molecular level of biological processes are based on noncovalent interactions. Interactions between metal atoms and proteins are based on noncovalent interactions that underlie the mechanisms involved in many cellular processes. The activities of enzymes are highly dependent on the interactions of such protein groups with cofactors, substrates, metal ions, and other proteins. The compositions and binding stoichiometry of protein-metal complexes can be determined with high accuracy performing mass spectrometry (MS) analysis. The conformational features of protein-metal complexes can be studied additionally using a mass spectrometer with ion mobility spectrometry (IMS) capability. This study focuses the monitoring the differences in the conformational changes of insulin protein during the formation of its complex with copper and alkali metals using trapped ion mobility spectrometry – time-of-flight (TIMS–TOF) mass spectrometer instrument. The compaction of the insulin structure by the formation of the insulin-copper complexes in the gas phase was determined with TIMS-TOF-MS analyses. However, no change was observed in the insulin structure with the addition of H, Na, and K atoms as adducts at the same analysis conditions.
Keywords
Noncovalent Interactions Protein-Metal Complexes Conformational Change Trapped Ion Mobility-Mass Spectrometry.
Supporting Institution
The Presidency of The Republic of Turkey, Presidency of Strategy and Budget
Project Number
2016 K 121230
Thanks
I would like to acknowledge Prof. Dr. Bekir Salih for his helpful discussions. The mass spectrometry laboratory is financially supported by the Presidency of the Republic of Turkey, Presidency of Strategy and Budget under project number 2016 K 121230.
References
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- E. Meggers, From conventional to unusual enzyme inhibitor scaffolds: the quest for target specificity, Angewandte Chemie International Edition 50(11) (2011) 2442-2448.
- S.J. Archibald, R. Smith, Protein‐Binding Metal Complexes: Noncovalent and Coordinative Interactions, Comprehensive Inorganic Chemistry II2013, pp. 661-682.
- L.A. Angel, Study of metal ion labeling of the conformational and charge states of lysozyme by ion mobility mass spectrometry, Eur J Mass Spectrom (Chichester) 17(3) (2011) 207-15.
- N. Potier, H. Rogniaux, G. Chevreux, A. Van Dorsselaer, Ligand–Metal Ion Binding to Proteins: Investigation by ESI Mass Spectrometry, Biological Mass Spectrometry2005, pp. 361-389.
- A.B. Ilesanmi, T.C. Moore, L.A. Angel, pH dependent chelation study of Zn(II) and Ni(II) by a series of hexapeptides using electrospray ionization – Ion mobility – Mass spectrometry, International Journal of Mass Spectrometry 455 (2020).
- J.A. Loo, R.R.O. Loo, H.R. Udseth, C.G. Edmonds, R.D. Smith, Solvent‐induced conformational changes of polypeptides probed by electrospray‐ionization mass spectrometry, Rapid Communications in Mass Spectrometry 5(3) (1991) 101-105.
- S.K. Chowdhury, V. Katta, B.T. Chait, An electrospray‐ionization mass spectrometer with new features, Rapid Communications in Mass Spectrometry 4(3) (1990) 81-87.
- E.N. Yousef, L.A. Angel, Comparison of the pH-dependent formation of His and Cys heptapeptide complexes of nickel(II), copper(II), and zinc(II) as determined by ion mobility-mass spectrometry, J Mass Spectrom 55(3) (2020) e4489.
- J.A. Loo, Studying noncovalent protein complexes by electrospray ionization mass spectrometry, Mass spectrometry reviews 16(1) (1997) 1-23.
- S. Banerjee, S. Mazumdar, Electrospray ionization mass spectrometry: a technique to access the information beyond the molecular weight of the analyte, International journal of analytical chemistry 2012 (2012).
- R. Mukherjee, The bioinorganic chemistry of copper, (2003).
- Z. Zhang, H. Wang, M. Yan, H. Wang, C. Zhang, Novel copper complexes as potential proteasome inhibitors for cancer treatment (Review), Mol Med Rep 15(1) (2017) 3-11.
- H. Tapiero, D.á. Townsend, K. Tew, Trace elements in human physiology and pathology. Copper, Biomedicine & pharmacotherapy 57(9) (2003) 386-398.
- Z. Fu, E. R Gilbert, D. Liu, Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes, Current diabetes reviews 9(1) (2013) 25-53.
- A.R. Saltiel, C.R. Kahn, Insulin signalling and the regulation of glucose and lipid metabolism, Nature 414(6865) (2001) 799-806.
- M. Gülfen, A. Özdemir, J.L. Lin, C.H. Chen, Investigation of non‐covalent complexations of Ca (II) and Mg (II) ions with insulin by using electrospray ionization mass spectrometry, Rapid Communications in Mass Spectrometry 30(19) (2016) 2171-2182.
- M. Gülfen, A. Özdemir, J.-L. Lin, C.-H. Chen, Quantifying Na (I)-insulin and K (I)-insulin non-covalent complexes by ESI–MS method and calculation of their equilibrium constants, International Journal of Biological Macromolecules 103 (2017) 910-918.
- M.F. Dunn, Zinc–ligand interactions modulate assembly and stability of the insulin hexamer–a review, Biometals 18(4) (2005) 295-303.
- M. Gulfen, A. Ozdemir, C.H. Chen, Monitoring Silver(I)-Insulin Complexes with Electrospray Ionization Quadrupole Ion Trap Mass Spectrometry, J Am Soc Mass Spectrom (2021).
- J.M. Spraggins, K.V. Djambazova, E.S. Rivera, L.G. Migas, E.K. Neumann, A. Fuetterer, J. Suetering, N. Goedecke, A. Ly, R. Van de Plas, High-performance molecular imaging with MALDI trapped ion-mobility time-of-flight (timsTOF) mass spectrometry, Analytical chemistry 91(22) (2019) 14552-14560.
- C.G. Vasilopoulou, K. Sulek, A.-D. Brunner, N.S. Meitei, U. Schweiger-Hufnagel, S.W. Meyer, A. Barsch, M. Mann, F. Meier, Trapped ion mobility spectrometry and PASEF enable in-depth lipidomics from minimal sample amounts, Nature communications 11(1) (2020) 1-11.
- L.V. Tose, P. Benigni, D. Leyva, A. Sundberg, C.E. Ramirez, M.E. Ridgeway, M.A. Park, W. Romao, R. Jaffe, F. Fernandez-Lima, Coupling trapped ion mobility spectrometry to mass spectrometry: trapped ion mobility spectrometry-time-of-flight mass spectrometry versus trapped ion mobility spectrometry-Fourier transform ion cyclotron resonance mass spectrometry, Rapid Commun Mass Spectrom 32(15) (2018) 1287-1295.
- M. Weiss, D.F. Steiner, L.H. Philipson, Insulin biosynthesis, secretion, structure, and structure-activity relationships, (2015).
- M.E. Ridgeway, M. Lubeck, J. Jordens, M. Mann, M.A. Park, Trapped ion mobility spectrometry: A short review, International Journal of Mass Spectrometry 425 (2018) 22-35.
- E.A. Mason, E.W. McDaniel, Transport properties of ions in gases, Wiley Online Library1988.
- T. Wyttenbach, M. Grabenauer, K. Thalassinos, J.H. Scrivens, M.T. Bowers, The effect of calcium ions and peptide ligands on the relative stabilities of the calmodulin dumbbell and compact structures, The Journal of Physical Chemistry B 114(1) (2010) 437-447.
- T.G. Flick, S.I. Merenbloom, E.R. Williams, Effects of metal ion adduction on the gas-phase conformations of protein ions, Journal of the American Society for Mass Spectrometry 24(11) (2013) 1654-1662.
- T. Solouki, R. Fort, A. Alomary, A. Fattahi, Gas phase hydrogen deuterium exchange reactions of a model peptide: FT-ICR and computational analyses of metal induced conformational mutations, Journal of the American Society for Mass Spectrometry 12(12) (2001) 1272-1285.
- E.M. Martin, F.D. Kondrat, A.J. Stewart, J.H. Scrivens, P.J. Sadler, C.A. Blindauer, Native electrospray mass spectrometry approaches to probe the interaction between zinc and an anti-angiogenic peptide from histidine-rich glycoprotein, Scientific reports 8(1) (2018) 1-13.
- A. Noor, S. Qayyum, F. Jabeen, A.U. Rehman, Mononuclear Tricoordinate Copper (I) and Silver (I) Halide Complexes of a Sterically Bulky Thiourea Ligand and a Computational Insight of Their Interaction with Human Insulin, Molecules 27(13) (2022) 4231.
Tuzaklamalı İyon Hareketliliği-Kütle Spektrometrisi Tekniği Kullanılarak İnsülinin Bakır ve Alkali Metal Komplekslerinin Konformasyonel Farklılıklarının Analizi
Abstract
Moleküler tanıma, protein katlanması ve supramoleküler yapıların oluşumu gibi moleküler düzeyde meydana gelen biyolojik süreçler kovalent olmayan etkileşimlere dayanır. Metal atomları ve proteinler arasındaki etkileşimler de birçok hücresel süreçte yer alan mekanizmaların temelini oluşturan kovalent olmayan etkileşimlere dayanmaktadır. Enzimlerin aktiviteleri, bu tür protein gruplarının kofaktörler, substratlar, metal iyonları ve diğer proteinlerle olan etkileşimlerine büyük ölçüde bağlıdır. Protein-metal komplekslerinin bileşimleri ve bağlanma stokiyometrileri, yüksek doğrulukta kütle spektrometrik (MS) analiz ile belirlenebilir. Protein-metal komplekslerinin konformasyonel özellikleri ise iyon hareketliliği spektrometrisi (IMS) özelliğine sahip bir kütle spektrometresi kullanılarak ek olarak incelenebilmektedir. Bu çalışmada tuzaklamalı iyon hareketliliği spektrometrisi - uçuş zamanlı (TIMS-TOF) kütle spektrometresi kullanılarak bakır ve alkali metallerle komplekslerinin oluşumu sırasında insülin proteininin konformasyonel değişimlerindeki farklılıkların izlenmesine odaklanılmaktadır. İnsülin-bakır komplekslerinin oluşmasıyla insülin yapısının gaz fazında daha kompakt hale geldiği TIMS-TOF-MS analizleri ile belirlenmiştir. Ancak aynı analiz koşullarında H, Na ve K atomlarının eklenmesiyle insülin yapısında herhangi bir değişiklik gözlenmemiştir.
Keywords
Kovalent olmayan etkileşimler Protein-metal kompleksleri Konformasyonel Değişim Tuzaklamalı iyon hareketliliği- kütle spektrometrisi
Project Number
2016 K 121230
References
- C.M. Crittenden, E.T. Novelli, M.R. Mehaffey, G.N. Xu, D.H. Giles, W.A. Fies, K.N. Dalby, L.J. Webb, J.S. Brodbelt, Structural Evaluation of Protein/Metal Complexes via Native Electrospray Ultraviolet Photodissociation Mass Spectrometry, J Am Soc Mass Spectrom 31(5) (2020) 1140-1150.
- E. Meggers, From conventional to unusual enzyme inhibitor scaffolds: the quest for target specificity, Angewandte Chemie International Edition 50(11) (2011) 2442-2448.
- S.J. Archibald, R. Smith, Protein‐Binding Metal Complexes: Noncovalent and Coordinative Interactions, Comprehensive Inorganic Chemistry II2013, pp. 661-682.
- L.A. Angel, Study of metal ion labeling of the conformational and charge states of lysozyme by ion mobility mass spectrometry, Eur J Mass Spectrom (Chichester) 17(3) (2011) 207-15.
- N. Potier, H. Rogniaux, G. Chevreux, A. Van Dorsselaer, Ligand–Metal Ion Binding to Proteins: Investigation by ESI Mass Spectrometry, Biological Mass Spectrometry2005, pp. 361-389.
- A.B. Ilesanmi, T.C. Moore, L.A. Angel, pH dependent chelation study of Zn(II) and Ni(II) by a series of hexapeptides using electrospray ionization – Ion mobility – Mass spectrometry, International Journal of Mass Spectrometry 455 (2020).
- J.A. Loo, R.R.O. Loo, H.R. Udseth, C.G. Edmonds, R.D. Smith, Solvent‐induced conformational changes of polypeptides probed by electrospray‐ionization mass spectrometry, Rapid Communications in Mass Spectrometry 5(3) (1991) 101-105.
- S.K. Chowdhury, V. Katta, B.T. Chait, An electrospray‐ionization mass spectrometer with new features, Rapid Communications in Mass Spectrometry 4(3) (1990) 81-87.
- E.N. Yousef, L.A. Angel, Comparison of the pH-dependent formation of His and Cys heptapeptide complexes of nickel(II), copper(II), and zinc(II) as determined by ion mobility-mass spectrometry, J Mass Spectrom 55(3) (2020) e4489.
- J.A. Loo, Studying noncovalent protein complexes by electrospray ionization mass spectrometry, Mass spectrometry reviews 16(1) (1997) 1-23.
- S. Banerjee, S. Mazumdar, Electrospray ionization mass spectrometry: a technique to access the information beyond the molecular weight of the analyte, International journal of analytical chemistry 2012 (2012).
- R. Mukherjee, The bioinorganic chemistry of copper, (2003).
- Z. Zhang, H. Wang, M. Yan, H. Wang, C. Zhang, Novel copper complexes as potential proteasome inhibitors for cancer treatment (Review), Mol Med Rep 15(1) (2017) 3-11.
- H. Tapiero, D.á. Townsend, K. Tew, Trace elements in human physiology and pathology. Copper, Biomedicine & pharmacotherapy 57(9) (2003) 386-398.
- Z. Fu, E. R Gilbert, D. Liu, Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes, Current diabetes reviews 9(1) (2013) 25-53.
- A.R. Saltiel, C.R. Kahn, Insulin signalling and the regulation of glucose and lipid metabolism, Nature 414(6865) (2001) 799-806.
- M. Gülfen, A. Özdemir, J.L. Lin, C.H. Chen, Investigation of non‐covalent complexations of Ca (II) and Mg (II) ions with insulin by using electrospray ionization mass spectrometry, Rapid Communications in Mass Spectrometry 30(19) (2016) 2171-2182.
- M. Gülfen, A. Özdemir, J.-L. Lin, C.-H. Chen, Quantifying Na (I)-insulin and K (I)-insulin non-covalent complexes by ESI–MS method and calculation of their equilibrium constants, International Journal of Biological Macromolecules 103 (2017) 910-918.
- M.F. Dunn, Zinc–ligand interactions modulate assembly and stability of the insulin hexamer–a review, Biometals 18(4) (2005) 295-303.
- M. Gulfen, A. Ozdemir, C.H. Chen, Monitoring Silver(I)-Insulin Complexes with Electrospray Ionization Quadrupole Ion Trap Mass Spectrometry, J Am Soc Mass Spectrom (2021).
- J.M. Spraggins, K.V. Djambazova, E.S. Rivera, L.G. Migas, E.K. Neumann, A. Fuetterer, J. Suetering, N. Goedecke, A. Ly, R. Van de Plas, High-performance molecular imaging with MALDI trapped ion-mobility time-of-flight (timsTOF) mass spectrometry, Analytical chemistry 91(22) (2019) 14552-14560.
- C.G. Vasilopoulou, K. Sulek, A.-D. Brunner, N.S. Meitei, U. Schweiger-Hufnagel, S.W. Meyer, A. Barsch, M. Mann, F. Meier, Trapped ion mobility spectrometry and PASEF enable in-depth lipidomics from minimal sample amounts, Nature communications 11(1) (2020) 1-11.
- L.V. Tose, P. Benigni, D. Leyva, A. Sundberg, C.E. Ramirez, M.E. Ridgeway, M.A. Park, W. Romao, R. Jaffe, F. Fernandez-Lima, Coupling trapped ion mobility spectrometry to mass spectrometry: trapped ion mobility spectrometry-time-of-flight mass spectrometry versus trapped ion mobility spectrometry-Fourier transform ion cyclotron resonance mass spectrometry, Rapid Commun Mass Spectrom 32(15) (2018) 1287-1295.
- M. Weiss, D.F. Steiner, L.H. Philipson, Insulin biosynthesis, secretion, structure, and structure-activity relationships, (2015).
- M.E. Ridgeway, M. Lubeck, J. Jordens, M. Mann, M.A. Park, Trapped ion mobility spectrometry: A short review, International Journal of Mass Spectrometry 425 (2018) 22-35.
- E.A. Mason, E.W. McDaniel, Transport properties of ions in gases, Wiley Online Library1988.
- T. Wyttenbach, M. Grabenauer, K. Thalassinos, J.H. Scrivens, M.T. Bowers, The effect of calcium ions and peptide ligands on the relative stabilities of the calmodulin dumbbell and compact structures, The Journal of Physical Chemistry B 114(1) (2010) 437-447.
- T.G. Flick, S.I. Merenbloom, E.R. Williams, Effects of metal ion adduction on the gas-phase conformations of protein ions, Journal of the American Society for Mass Spectrometry 24(11) (2013) 1654-1662.
- T. Solouki, R. Fort, A. Alomary, A. Fattahi, Gas phase hydrogen deuterium exchange reactions of a model peptide: FT-ICR and computational analyses of metal induced conformational mutations, Journal of the American Society for Mass Spectrometry 12(12) (2001) 1272-1285.
- E.M. Martin, F.D. Kondrat, A.J. Stewart, J.H. Scrivens, P.J. Sadler, C.A. Blindauer, Native electrospray mass spectrometry approaches to probe the interaction between zinc and an anti-angiogenic peptide from histidine-rich glycoprotein, Scientific reports 8(1) (2018) 1-13.
- A. Noor, S. Qayyum, F. Jabeen, A.U. Rehman, Mononuclear Tricoordinate Copper (I) and Silver (I) Halide Complexes of a Sterically Bulky Thiourea Ligand and a Computational Insight of Their Interaction with Human Insulin, Molecules 27(13) (2022) 4231.
Details
| Primary Language | English |
|---|---|
| Subjects | Engineering |
| Journal Section | Research Article |
| Authors | |
| Project Number | 2016 K 121230 |
| Publication Date | January 1, 2023 |
| Acceptance Date | October 14, 2022 |
| Published in Issue | Year 2023 Volume: 51 Issue: 1 |
Cite
HACETTEPE JOURNAL OF BIOLOGY AND CHEMİSTRY
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