Conformational Selection of α-Synuclein Tetramers at Biological Interfaces.

ABSTRACT: Controlling the polymorphic assemblies of α-synuclein (αS) oligomers is crucial to reroute toxic protein aggregation implicated in Parkinson's disease (PD). One potential mediator is the interaction of αS tetramers with cell membranes, which may regulate the dynamic balance between aggregation-prone disordered monomers and aggregation-resistant helical tetramers. Here, we model diverse tetramer-cell interactions and compare the structure-function relations at the supramolecular-biological interface with available experimental data. The models predict preferential interaction of compact αS tetramers with highly charged membrane surfaces, which may further stabilize this aggregation-resistant conformer. On moderately charged membranes, extended structures are preferred. In addition to surfac

SUBMITTER: Bhattacharya S 

PROVIDER: S-EPMC11523075 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature