Mechanistic Insight into the Suppression of Polyglutamine Aggregation by SRCP1.

ABSTRACT: Protein aggregation is a hallmark of the polyglutamine diseases. One potential treatment for these diseases is suppression of polyglutamine aggregation. Previous work identified the cellular slime mold Dictyostelium discoideum as being naturally resistant to polyglutamine aggregation. Further work identified serine-rich chaperone protein 1 (SRCP1) as a protein that is both necessary in Dictyostelium and sufficient in human cells to suppress polyglutamine aggregation. Therefore, understanding how SRCP1 suppresses aggregation may be useful for developing therapeutics for the polyglutamine diseases. Here we utilized a de novo protein modeling approach to generate predictions of SRCP1's structure. Using our best-fit model, we generated mutants that were predicted to alter

SUBMITTER: Haver HN 

PROVIDER: S-EPMC10023506 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature