Coupling of the non-amyloid-component (NAC) domain and the KTK(E/Q)GV repeats stabilize the α-synuclein fibrils.

ABSTRACT: The aggregates of α-synuclein (αS) are a major pathological hallmark of Parkinson's disease (PD) making their structure-function relationship important for rational drug design. Yet, the atomic structure of the αS aggregates is unavailable, making it difficult to understand the underlying aggregation mechanism. In this work, based on available experimental data, we examined plausible molecular structures of αS(20/30-110) fibrils for the first time by employing computational approaches. The optimized structure was used to investigate possible interactions with aggregation inhibitors. Our structural models characterize the essential properties of the five-layered fold of the αS fibril. The distribution of the β-strands and the topology of the five β-strands in the relatively stable models ar

SUBMITTER: Xu L 

PROVIDER: S-EPMC4960003 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature