A Proposed Atomic Structure of the Self-Assembly of the Non-Amyloid-β Component of Human α-Synuclein As Derived by Computational Tools

Yoav Atsmon-Raz, Yifat Miller

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

α-Synuclein (AS) fibrils are the major hallmarks of Parkinsons disease (PD). It is known that the central domain of the 140-residue AS protein, known as the non-amyloid-β component (NAC), plays a crucial role in aggregation. The secondary structure of AS fibrils (including the NAC domain) has been proposed on the basis of solid-state nuclear magnetic resonance studies, but the atomic structure of the self-assembly of NAC (or AS itself) is still elusive. This is the first study that presents a detailed three-dimensional structure of NAC at atomic resolution. The proposed self-assembled structure of NAC consists of three β-strands connected by two turn regions. Our study shows that calculated structural parameter values of the simulated fibril-like cross-β structure of NAC are in excellent agreement with the experimental values. Moreover, the diameter dimensions of the proposed fibril-like structure are also in agreement with experimental measurements. The proposed fibril-like structure of NAC may assist in future work aimed at understanding the formation of aggregates in PD and developing compounds to modulate aggregation.

Original languageEnglish
Pages (from-to)10005-10015
Number of pages11
JournalJournal of Physical Chemistry B
Volume119
Issue number31
DOIs
StatePublished - 6 Aug 2015

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