Mapping the sequence specificity of heterotypic amyloid interactions enables the identification of aggregation modifiers.

ABSTRACT: Heterotypic amyloid interactions between related protein sequences have been observed in functional and disease amyloids. While sequence homology seems to favour heterotypic amyloid interactions, we have no systematic understanding of the structural rules determining such interactions nor whether they inhibit or facilitate amyloid assembly. Using structure-based thermodynamic calculations and extensive experimental validation, we performed a comprehensive exploration of the defining role of sequence promiscuity in amyloid interactions. Using tau as a model system we demonstrate that proteins with local sequence homology to tau amyloid nucleating regions can modify fibril nucleation, morphology, assembly and spreading of aggregates in cultured cells. Depending on the type of mutation such i

SUBMITTER: Louros N 

PROVIDER: S-EPMC8924238 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature