title: A Proposed Atomic Structure of the Self-Assembly of the Non-Amyloid-β Component of Human α-Synuclein As Derived by Computational Tools.
abstract: α-Synuclein (AS) fibrils are the major hallmarks of Parkinson's 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.
authors.affiliation: †Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.|‡Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Atsmon-Raz
authors.affiliation: †Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.|‡Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
authors.forename: Yifat
authors.initials: Y
authors.lastname: Miller
mesh_terms: D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D051844:alpha-Synuclein