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

William M. Jacobs; Tuomas P. J. Knowles; Daan Frenkel

doi:10.1371/journal.pcbi.1004756

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arXiv · 1508.07924

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

William M. Jacobs·Tuomas P. J. Knowles·Daan Frenkel

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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.

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William M. Jacobs, Tuomas P. J. Knowles, Daan Frenkel. 2016-02-12. Oligomers of heat-shock proteins: Structures that don't imply function. https://doi.org/10.1371/journal.pcbi.1004756

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