Unknown

Dataset Information

0

Plasticity of Membrane Binding by the Central Region of α-Synuclein.


ABSTRACT: Membrane binding by α-synuclein (αS), an intrinsically disordered protein whose aggregation is associated with Parkinson's disease, is a key step in determining its biological properties under both physiological and pathological conditions. Upon membrane interaction, αS retains a partial level of structural disorder despite acquiring α-helical content. In the membrane-bound state, the equilibrium between the helical-bound and disordered-detached states of the central region of αS (residues 65-97) has been involved in a double-anchor mechanism that promotes the clustering of synaptic vesicles. Herein, we investigated the underlying molecular bases of this equilibrium using enhanced coarse-grained molecular dynamics simulations. The results enabled clarifying the conformational dependencies of the membrane affinity by this protein region that, in addition to playing a role in physiological membrane binding, has key relevance for the aggregation of αS and the mechanisms of the toxicity of the resulting assemblies.

SUBMITTER: Navarro-Paya C 

PROVIDER: S-EPMC9240306 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

altmetric image

Publications

Plasticity of Membrane Binding by the Central Region of α-Synuclein.

Navarro-Paya Carlos C   Sanz-Hernandez Maximo M   De Simone Alfonso A  

Frontiers in molecular biosciences 20220615


Membrane binding by α-synuclein (αS), an intrinsically disordered protein whose aggregation is associated with Parkinson's disease, is a key step in determining its biological properties under both physiological and pathological conditions. Upon membrane interaction, αS retains a partial level of structural disorder despite acquiring α-helical content. In the membrane-bound state, the equilibrium between the helical-bound and disordered-detached states of the central region of αS (residues 65-97  ...[more]

Similar Datasets

| S-EPMC3946565 | biostudies-literature
| S-EPMC7091477 | biostudies-literature
| S-EPMC4075992 | biostudies-literature
| S-EPMC6090819 | biostudies-literature
| S-EPMC7442712 | biostudies-literature
| S-EPMC9953312 | biostudies-literature
| S-EPMC4049638 | biostudies-literature
| S-EPMC6370759 | biostudies-literature
| S-EPMC11741239 | biostudies-literature
| S-EPMC3249522 | biostudies-literature