Autonomous aggregation suppression by acidic residues explains why chaperones favour basic residues.

ABSTRACT: Many chaperones favour binding to hydrophobic sequences that are flanked by basic residues while disfavouring acidic residues. However, the origin of this bias in protein quality control remains poorly understood. Here, we show that while acidic residues are the most efficient aggregation inhibitors, they are also less compatible with globular protein structure than basic amino acids. As a result, while acidic residues allow for chaperone-independent control of aggregation, their use is structurally limited. Conversely, we find that, while being more compatible with globular structure, basic residues are not sufficient to autonomously suppress protein aggregation. Using Hsp70, we show that chaperones with a bias towards basic residues are structurally adapted to prioritize aggregating sequ

SUBMITTER: Houben B 

PROVIDER: S-EPMC7265246 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature