Mechanistic Insights into the Polymorphic Associations and Cross-Seeding of Aβ and HIAPP in the Presence of Histidine Tautomerism: An All-Atom Molecular Dynamic Study

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Feb 26

PMID 35216047

Authors

Abbas Salimi

Sompriya Chatterjee

Jin Yong Lee

Affiliations

Soon will be listed here.

Abstract

Hundreds of millions of people around the world have been affected by Type 2 diabetes (T2D) which is a metabolic disorder. Clinical research has revealed T2D as a possible risk factor for Alzheimer's disease (AD) development (and vice versa). Amyloid-β (Aβ) and human islet amyloid polypeptide are the main pathological species in AD and T2D, respectively. However, the mechanisms by which these two amyloidogenic peptides co-aggregate are largely uninvestigated. Herein, for the first time, we present the cross-seeding between Amylin1-37 and Aβ40 considering the particular effect of the histidine tautomerism at atomic resolution applying the all-atom molecular dynamics (MD) simulations for heterodimeric complexes. The results via random seed MD simulations indicated that the Aβ40(δδδ) isomer in cross-talking with Islet(ε) and Islet(δ) isomers could retain or increase the β-sheet content in its structure that may make it more prone to further aggregation and exhibit higher toxicity. The other tautomeric isomers which initially did not have a β-sheet structure in their monomeric forms did not show any generated β-sheet, except for one seed of the Islet(ε) and Aβ40(εεε) heterodimers complex that displayed a small amount of formed β-sheet. This computational research may provide a different point of view to examine all possible parameters that may contribute to the development of AD and T2D and provide a better understanding of the pathological link between these two severe diseases.

References

Salimi A, Chatterjee S, Lee J . Histidine Tautomerism Driving Human Islet Amyloid Polypeptide Aggregation in the Early Stages of Diabetes Mellitus Progression: Insight at the Atomistic Level. Chem Asian J. 2021; 16(17):2453-2462. DOI: 10.1002/asia.202100641. View

Li H, Salimi A, Lee J . Intrinsic Origin of Amyloid Aggregation: Collective Effects of the Mutation and Tautomerism of Histidine. ACS Chem Neurosci. 2019; 10(11):4729-4734. DOI: 10.1021/acschemneuro.9b00491. View

Salimi A, Li H, Lee J . Molecular insight into the early stage of amyloid-β(1-42) Homodimers aggregation influenced by histidine tautomerism. Int J Biol Macromol. 2021; 184:887-897. DOI: 10.1016/j.ijbiomac.2021.06.078. View

ONuallain B, Williams A, Westermark P, Wetzel R . Seeding specificity in amyloid growth induced by heterologous fibrils. J Biol Chem. 2004; 279(17):17490-9. DOI: 10.1074/jbc.M311300200. View

Chatterjee S, Salimi A, Lee J . Intrinsic Origin of Tau Protein Aggregation: Effects of Histidine Tautomerism on Tau Monomer. ACS Chem Neurosci. 2020; 11(22):3814-3822. DOI: 10.1021/acschemneuro.0c00587. View

Mawuenyega K, Sigurdson W, Ovod V, Munsell L, Kasten T, Morris J . Decreased clearance of CNS beta-amyloid in Alzheimer's disease. Science. 2010; 330(6012):1774. PMC: 3073454. DOI: 10.1126/science.1197623. View

Brender J, Lee E, Hartman K, Wong P, Ramamoorthy A, Steel D . Biphasic effects of insulin on islet amyloid polypeptide membrane disruption. Biophys J. 2011; 100(3):685-692. PMC: 3030259. DOI: 10.1016/j.bpj.2010.09.070. View

Vila J, Arnautova Y, Vorobjev Y, Scheraga H . Assessing the fractions of tautomeric forms of the imidazole ring of histidine in proteins as a function of pH. Proc Natl Acad Sci U S A. 2011; 108(14):5602-7. PMC: 3078339. DOI: 10.1073/pnas.1102373108. View

Basith S, Manavalan B, Shin T, Lee G . A Molecular Dynamics Approach to Explore the Intramolecular Signal Transduction of PPAR-α. Int J Mol Sci. 2019; 20(7). PMC: 6479491. DOI: 10.3390/ijms20071666. View

10.

Berhanu W, Yasar F, Hansmann U . In silico cross seeding of Aβ and amylin fibril-like oligomers. ACS Chem Neurosci. 2013; 4(11):1488-500. PMC: 3837374. DOI: 10.1021/cn400141x. View

11.

Rezaei-Ghaleh N, Andreetto E, Yan L, Kapurniotu A, Zweckstetter M . Interaction between amyloid beta peptide and an aggregation blocker peptide mimicking islet amyloid polypeptide. PLoS One. 2011; 6(5):e20289. PMC: 3102090. DOI: 10.1371/journal.pone.0020289. View

12.

Ning L, Pan D, Zhang Y, Wang S, Liu H, Yao X . Effects of the Pathogenic Mutation A117V and the Protective Mutation H111S on the Folding and Aggregation of PrP106-126: Insights from Replica Exchange Molecular Dynamics Simulations. PLoS One. 2015; 10(5):e0125899. PMC: 4439087. DOI: 10.1371/journal.pone.0125899. View

13.

Chatterjee S, Salimi A, Lee J . Unraveling the Histidine Tautomerism Effect on the Initial Stages of Prion Misfolding: New Insights from a Computational Perspective. ACS Chem Neurosci. 2021; 12(17):3203-3213. DOI: 10.1021/acschemneuro.1c00376. View

14.

Ren B, Hu R, Zhang M, Liu Y, Xu L, Jiang B . Experimental and Computational Protocols for Studies of Cross-Seeding Amyloid Assemblies. Methods Mol Biol. 2018; 1777:429-447. PMC: 6456059. DOI: 10.1007/978-1-4939-7811-3_27. View

15.

Morgan J, Verkhovsky M, Wikstrom M . The histidine cycle: a new model for proton translocation in the respiratory heme-copper oxidases. J Bioenerg Biomembr. 1994; 26(6):599-608. DOI: 10.1007/BF00831534. View

16.

Nicolls M . The clinical and biological relationship between Type II diabetes mellitus and Alzheimer's disease. Curr Alzheimer Res. 2005; 1(1):47-54. DOI: 10.2174/1567205043480555. View

17.

Andreetto E, Yan L, Caporale A, Kapurniotu A . Dissecting the role of single regions of an IAPP mimic and IAPP in inhibition of Aβ40 amyloid formation and cytotoxicity. Chembiochem. 2011; 12(9):1313-22. DOI: 10.1002/cbic.201100192. View

18.

Humphrey W, Dalke A, Schulten K . VMD: visual molecular dynamics. J Mol Graph. 1996; 14(1):33-8, 27-8. DOI: 10.1016/0263-7855(96)00018-5. View

19.

Pettersen E, Goddard T, Huang C, Couch G, Greenblatt D, Meng E . UCSF Chimera--a visualization system for exploratory research and analysis. J Comput Chem. 2004; 25(13):1605-12. DOI: 10.1002/jcc.20084. View

20.

Oskarsson M, Paulsson J, Schultz S, Ingelsson M, Westermark P, Westermark G . In vivo seeding and cross-seeding of localized amyloidosis: a molecular link between type 2 diabetes and Alzheimer disease. Am J Pathol. 2015; 185(3):834-46. DOI: 10.1016/j.ajpath.2014.11.016. View