Electrostatically-guided inhibition of Curli amyloid nucleation by the CsgC-like family of chaperones.

ABSTRACT: Polypeptide aggregation into amyloid is linked with several debilitating human diseases. Despite the inherent risk of aggregation-induced cytotoxicity, bacteria control the export of amyloid-prone subunits and assemble adhesive amyloid fibres during biofilm formation. An Escherichia protein, CsgC potently inhibits amyloid formation of curli amyloid proteins. Here we unlock its mechanism of action, and show that CsgC strongly inhibits primary nucleation via electrostatically-guided molecular encounters, which expands the conformational distribution of disordered curli subunits. This delays the formation of higher order intermediates and maintains amyloidogenic subunits in a secretion-competent form. New structural insight also reveal that CsgC is part of diverse family of bacterial amyloid

SUBMITTER: Taylor JD 

PROVIDER: S-EPMC4838910 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature