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Experimental and Computational Protocols for Studies of Cross-Seeding Amyloid Assemblies

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Peptide Self-Assembly

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1777))

Abstract

Alzheimer’s disease (AD) and type 2 diabetes (T2D) are two common protein aggregation diseases. Compelling evidence has shown a link between AD and T2D, which may derive from interspecies cross-sequence interactions between amyloid-β peptide (Aβ), associated with AD, and human islet amyloid polypeptide (hIAPP), associated with T2D. Herein, we present experimental and computational protocols and tools to study the aggregate structures and kinetics, conformational conversion, and molecular interactions of Aβ-hIAPP mixtures. These protocols could be generally applied to other cross-seeding behaviors of amyloid peptides.

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References

  1. Chiti F, Dobson CM (2006) Protein misfolding, functional amyloid, and human disease. Annu Rev Biochem 75:333–366

    Article  CAS  Google Scholar 

  2. Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, Brett FM, Farrell MA, Rowan MJ, Lemere CA, Regan CM, Walsh DM, Sabatini BL, Selkoe DJ (2008) Amyloid-[beta] protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat Med 14(8):837–842

    Article  CAS  Google Scholar 

  3. DeToma AS, Salamekh S, Ramamoorthy A, Lim MH (2012) Misfolded proteins in Alzheimer’s disease and type II diabetes. Chem Soc Rev 41(2):608–621

    Article  CAS  Google Scholar 

  4. Janson J, Laedtke T, Parisi JE, O’Brien P, Petersen RC, Butler PC (2004) Increased risk of type 2 diabetes in Alzheimer disease. Diabetes 53(2):474–481

    Article  CAS  Google Scholar 

  5. Nicolls MR (2004) The clinical and biological relationship between type II diabetes Mellitus and Alzheimers disease. Curr Alzheimer Res 1(1):47–54

    Article  CAS  Google Scholar 

  6. Andreetto E, Yan LM, Tatarek-Nossol M, Velkova A, Frank R, Kapurniotu A (2010) Identification of hot regions of the A beta-IAPP interaction interface as high-affinity binding sites in both cross- and self-association. Angewandte Chemie Int Ed 49(17):3081–3085

    Article  CAS  Google Scholar 

  7. Miklossy J, Qing H, Radenovic A, Kis A, Vileno B, Laszlo F, Miller L, Martins RN, Waeber G, Mooser V, Bosman F, Khalili K, Darbinian N, McGeer PL (2010) Beta amyloid and hyperphosphorylated tau deposits in the pancreas in type 2 diabetes. Neurobiol Aging 31(9):1503–1515

    Article  CAS  Google Scholar 

  8. Luca S, Yau W-M, Leapman R, Tycko R (2007) Peptide conformation and supramolecular organization in amylin fibrils: constraints from solid-state NMR. Biochemistry 46(47):13505–13522

    Article  CAS  Google Scholar 

  9. Brender JR, Salamekh S, Ramamoorthy A (2012) Membrane disruption and early events in the aggregation of the diabetes related peptide IAPP from a molecular perspective. Acc Chem Res 45(3):454–462

    Article  CAS  Google Scholar 

  10. Zhang MZ, Hu RD, Chen H, Chang Y, Ma J, Liang GZ, Mi JY, Wang YR, Zheng J (2015) Polymorphic cross-seeding amyloid assemblies of amyloid-beta and human islet amyloid polypeptide. Phys Chem Chem Phys 17(35):23245–23256

    Article  CAS  Google Scholar 

  11. Zhang M, Hu R, Chen H, Chang Y, Gong X, Liu F, Zheng J (2015) Interfacial interaction and lateral association of cross-seeding assemblies between hIAPP and rIAPP oligomers. Phys Chem Chem Phys 17:10373–10382

    Article  CAS  Google Scholar 

  12. Nicolls MR (2004) The clinical and biological relationship between Type II diabetes Mellitus and Alzheimer’s disease. Curr Alzheimer Res 1(1):47–54

    Article  CAS  Google Scholar 

  13. Mandal PK, Pettegrew JW, Masliah E, Hamilton RL, Mandal R (2006) Interaction between Aβ peptide and α synuclein: molecular mechanisms in overlapping pathology of Alzheimer’s and Parkinson’s in dementia with Lewy body disease. Neurochem Res 31(9):1153–1162

    Article  CAS  Google Scholar 

  14. Stancu I-C, Vasconcelos B, Terwel D, Dewachter I (2014) Models of β-amyloid induced Tau-pathology: the long and “folded” road to understand the mechanism. Mol Neurodegener 9(1):1–14

    Article  Google Scholar 

  15. Liu P, Zhang S, Chen M-s, Liu Q, Wang C, Wang C, Li Y-M, Besenbacher F, Dong M (2012) Co-assembly of human islet amyloid polypeptide (hIAPP)/insulin. Chem Commun 48(2):191–193

    Article  CAS  Google Scholar 

  16. Hartman K, Brender JR, Monde K, Ono A, Evans ML, Popovych N, Chapman MR (2013) Ramamoorthy, A., Bacterial curli protein promotes the conversion of PAP248-286 into the amyloid SEVI: cross-seeding of dissimilar amyloid sequences. PeerJ 1:e5

    Article  Google Scholar 

  17. Andreetto E, Yan L-M, Tatarek-Nossol M, Velkova A, Frank R, Kapurniotu A (2010) Identification of hot regions of the Aβ–IAPP interaction interface as high-affinity binding sites in both cross- and self-association. Ange Chem Inter Ed 49(17):3081–3085

    Article  CAS  Google Scholar 

  18. O’Nuallain B, Williams AD, Westermark P, Wetzel R (2004) Seeding specificity in amyloid growth induced by heterologous fibrils. J Biol Chem 279(17):17490–17499

    Article  Google Scholar 

  19. Yan LM, Velkova A, Tatarek-Nossol M, Andreetto E, Kapurniotu A (2007) IAPP mimic blocks Aβ cytotoxic self-assembly: cross-suppression of amyloid toxicity of Aβ and IAPP suggests a molecular link between Alzheimer’s disease and type II diabetes. Angew Chem Int Ed 46(8):1246–1252

    Article  CAS  Google Scholar 

  20. Seeliger J, Evers F, Jeworrek C, Kapoor S, Weise K, Andreetto E, Tolan M, Kapurniotu A, Winter R (2012) Cross-amyloid interaction of Aβ and IAPP at lipid membranes. Angew Chem Int Ed 51(3):679–683

    Article  CAS  Google Scholar 

  21. Ma B, Nussinov R (2012) Selective molecular recognition in amyloid growth and transmission and cross-species barriers. J Mol Biol 421(2–3):172–184

    Article  CAS  Google Scholar 

  22. Hu R, Zhang M, Patel K, Wang Q, Chang Y, Gong X, Zhang G, Zheng J (2014) Cross-sequence interactions between human and rat islet amyloid polypeptides. Langmuir 30(18):5193–5201

    Article  CAS  Google Scholar 

  23. Hu R, Zhang M, Chen H, Jiang B, Zheng J (2015) Cross-seeding interaction between β-amyloid and human islet amyloid polypeptide. ACS Chem Neurosci 6(10):1759–1768

    Article  CAS  Google Scholar 

  24. Biancalana M, Makabe K, Koide A, Koide S (2009) Molecular mechanism of thioflavin-t binding to the surface of [beta]-rich peptide self-assemblies. J Mol Biol 385(4):1052–1063

    Article  CAS  Google Scholar 

  25. Sreerama N, Woody RW (2000) Estimation of protein secondary structure from circular dichroism spectra: comparison of CONTIN, SELCON, and CDSSTR methods with an expanded reference set. Anal Biochem 287(2):252–260

    Article  CAS  Google Scholar 

  26. Juszczyk P, Kolodziejczyk A, Grzonka Z (2005) Circular dichroism and aggregation studies of amyloid beta (11-28) fragment and its variants. Acta Biochim Pol 52(2):425

    CAS  PubMed  Google Scholar 

  27. Wang Q, Yu X, Patal K, Hu R, Chuang S, Zhang G, Zheng J (2013) Tanshinones inhibit amyloid aggregation by amyloid-β peptide, disaggregate amyloid fibrils, and protect cultured cells. ACS Chem Neurosci 4(6):1004–1015

    Article  CAS  Google Scholar 

  28. Luhrs T, Ritter C, Adrian M, Riek-Loher D, Bohrmann B, Doeli H, Schubert D, Riek R (2005) 3D structure of Alzheimer’s amyloid-beta(1-42) fibrils. Proc Natl Acad Sci U S A 102(48):17342–17347

    Article  CAS  Google Scholar 

  29. Luca S, Yau WM, Leapman R, Tycko R (2007) Peptide conformation and supramolecular organization in amylin fibrils: constraints from solid-state NMR. Biochemistry 46(47):13505–13522

    Article  CAS  Google Scholar 

  30. Zhang MZ, Hu RD, Chen H, Gong X, Zhou FM, Zhang L, Zheng J (2015) Polymorphic associations and structures of the cross-seeding of A beta(1-42) and hIAPP(1-37) polypeptides. J Chem Inf Model 55(8):1628–1639

    Article  CAS  Google Scholar 

  31. Van der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJC (2005) GROMACS: fast, flexible, and free. J Comput Chem 26(16):1701–1718

    Article  Google Scholar 

  32. Buck M, Bouguet-Bonnet S, Pastor RW, MacKerell AD (2006) Importance of the CMAP correction to the CHARMM22 protein force field: dynamics of hen lysozyme. Biophys J 90(4):L36–L38

    Article  CAS  Google Scholar 

  33. Yu X, Zheng J (2011) Polymorphic structures of Alzheimer’s β-amyloid globulomers. PLoS One 6(6):e20575

    Article  CAS  Google Scholar 

  34. Zhao J, Hu R, Sciacca MFM, Brender JR, Chen H, Ramamoorthy A, Zheng J (2014) Non-selective ion channel activity of polymorphic human islet amyloid polypeptide (amylin) double channels. Phys Chem Chem Phys 16(6):2368–2377

    Article  CAS  Google Scholar 

  35. Zhang MZ, Hu RD, Liang GZ, Chang Y, Sun Y, Peng ZM, Zheng J (2014) Structural and energetic insight into the cross-seeding amyloid assemblies of Human IAPP and Rat IAPP. J Phys Chem B 118(25):7026–7036

    Article  CAS  Google Scholar 

Download references

Acknowledgments

J.Z. thanks the financial support from NSF (CBET-1510099 and DMR-1607475), Alzheimer Association (2015-NIRG-341372), and National Natural Science Foundation of China (NSFC-21528601). The high-performance computational facilities of the Biowulf PC/Linux cluster at the NIH were mainly used for the simulations. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

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Author notes

  1. Baiping Ren and Rundong Hu contributed equally to this work.

Authors and Affiliations

  1. Department of Chemical & Biomolecular Engineering, The University of Akron, Akron, OH, USA

    Baiping Ren, Rundong Hu, Mingzhen Zhang, Yonglan Liu, Lijian Xu, Binbo Jiang, Jie Ma & Jie Zheng

  2. College of Life Sciences and Chemistry Hunan University of Technology, Zhuzhou, China

    Lijian Xu

  3. College of Chemical and Biological Engineering, Zhejiang University, Zhejiang, Hangzhou, China

    Binbo Jiang

  4. State Key Laboratory of Pollution Control and Resource Reuse, School of Environmental Science and Engineering, Tongji University, Shanghai, China

    Jie Ma

  5. Basic Science Program, Leidos Biomedical Research, Inc., Cancer and Inflammation Program, National Cancer Institute, Frederick, MD, USA

    Buyong Ma & Ruth Nussinov

  6. Sackler Institute of Molecular Medicine, Department of Human Genetics and Molecular Medicine Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Ruth Nussinov

Authors
  1. Baiping Ren
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  2. Rundong Hu
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  3. Mingzhen Zhang
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  4. Yonglan Liu
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  5. Lijian Xu
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  6. Binbo Jiang
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  7. Jie Ma
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  8. Buyong Ma
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  9. Ruth Nussinov
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  10. Jie Zheng
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Corresponding authors

Correspondence to Ruth Nussinov or Jie Zheng .

Editor information

Editors and Affiliations

  1. Department of Chemistry, University of Rochester, Rochester, New York, USA

    Bradley L. Nilsson

  2. Department of Medicinal Chemistry, Institute for Translational Neuroscience, University of Minnesota, Minneapolis, Minnesota, USA

    Todd M. Doran

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Ren, B. et al. (2018). Experimental and Computational Protocols for Studies of Cross-Seeding Amyloid Assemblies. In: Nilsson, B., Doran, T. (eds) Peptide Self-Assembly. Methods in Molecular Biology, vol 1777. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7811-3_27

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  • DOI: https://doi.org/10.1007/978-1-4939-7811-3_27

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7809-0

  • Online ISBN: 978-1-4939-7811-3

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