Study of Molecular Mechanisms of α-Synuclein Assembly: Insight into a Cross-β Structure in the N-Termini of New α-Synuclein Fibrils

ACS Omega
Daniel Nir Bloch, Yifat Miller

Abstract

Parkinson's disease is characterized by the self-assembly of α-synuclein (AS), in which its aggregates accumulate in the substantia nigra. The molecular mechanisms of the self-assembly of AS are challenging because AS is a relatively large intrinsically disordered protein, consisting of 140 residues. It is known that the N-termini of AS contribute to the toxicity of the proteins; therefore, it is important to investigate the self-assembly structure of the N-termini on AS as well. There have been extensive efforts to investigate the structural fibrils of AS(1-140), which have shown that the N-termini are disordered and do not participate in the fibrillary structure. This study illustrates for the first time that the N-termini of AS play a crucial role in the self-assembly of AS. This study reveals a new structure of AS(1-140) fibrils, in which the N-termini are essential parts of the cross-β structure of the fibrillary structure. This study suggests that there are polymorphic states of the self-assembled AS(1-140). While the polymorphic states of the N-termini do not participate in the fibrillary structure and fluctuate, our predicted new fibrillary structure of the N-termini not only participates in the fibrillary structure but...Continue Reading

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Citations

Oct 10, 2019·Physical Chemistry Chemical Physics : PCCP·Abhilash Sahoo, Silvina Matysiak
Jan 27, 2018·Physical Chemistry Chemical Physics : PCCP·Liang XuDamien Thompson
Jun 27, 2018·Proceedings of the National Academy of Sciences of the United States of America·Francesco Simone RuggeriGiovanni Dietler
Jan 10, 2018·Chemical Communications : Chem Comm·Conor M Haney, E James Petersson
Dec 20, 2017·The Journal of Physical Chemistry. B·Xavier PerioleSiewert J Marrink
Jan 20, 2022·ACS Chemical Neuroscience·Sapir Lan-Mark, Yifat Miller

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Methods Mentioned

BETA
nuclear magnetic resonance
NMR
ssNMR

Software Mentioned

ssNMR
Define Structure of Proteins ( DSSP )
GBMV
Accelrys Discovery Studio

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