Increased surface charge in the protein chaperone Spy enhances its anti-aggregation activity.

ABSTRACT: Chaperones are essential components of the protein homeostasis network. There is a growing interest in optimizing chaperone function, but exactly how to achieve this aim is unclear. Here, using a model chaperone, the bacterial protein Spy, we demonstrate that substitutions that alter the electrostatic potential of Spy's concave, client-binding surface enhance Spy's anti-aggregation activity. We show that this strategy is more efficient than one that enhances the hydrophobicity of Spy's surface. Our findings thus challenge the traditional notion that hydrophobic interactions are the major driving forces that guide chaperone-substrate binding. Kinetic data revealed that both charge- and hydrophobicity-enhanced Spy variants release clients more slowly, resulting in a greater "holdase" activit

SUBMITTER: He W 

PROVIDER: S-EPMC7573262 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature