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

Daniel Nir Bloch, Yifat Miller

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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 also stabilizes the fibrillary structure.

Original languageEnglish
Pages (from-to)3363-3370
Number of pages8
JournalACS Omega
Volume2
Issue number7
DOIs
StatePublished - 31 Jul 2017

ASJC Scopus subject areas

  • Chemistry (all)
  • Chemical Engineering (all)

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