Oligomers of heat-shock proteins: Structures that don't imply function

TL;DR

This study uses lattice model simulations to explore how passive molecular chaperones, like small heat-shock proteins, enhance protein solubility and form oligomers without necessarily implying functional significance.

Contribution

The paper demonstrates that weakly bound chaperone oligomers naturally form as a side-effect of optimizing proteome stability, without implying functional roles.

Findings

Chaperone binding strength can increase proteome solubility.

Weakly bound chaperone oligomers form under optimal conditions.

Oligomer formation does not significantly impact thermodynamic stability.

Abstract

Most proteins must remain soluble in the cytosol in order to perform their biological functions. To protect against undesired protein aggregation, living cells maintain a population of molecular chaperones that ensure the solubility of the proteome. Here we report simulations of a lattice model of interacting proteins to understand how low concentrations of passive molecular chaperones, such as small heat-shock proteins, suppress thermodynamic instabilities in protein solutions. Given fixed concentrations of chaperones and client proteins, the solubility of the proteome can be increased by tuning the chaperone--client binding strength. Surprisingly, we find that the binding strength that optimizes solubility while preventing irreversible chaperone binding also promotes the formation of weakly bound chaperone oligomers, although the presence of these oligomers does not significantly affect the thermodynamic stability of the solution. Such oligomers are commonly observed in experiments on small heat-shock proteins, but their connection to the biological function of these chaperones has remained unclear. Our simulations suggest that this clustering may not have any essential biological function, but rather emerges as a natural side-effect of optimizing the thermodynamic stability of the proteome.