Oligomers of Heat-Shock Proteins: Structures That Don't Imply Function

摘要

Author Summary The vast majority of living cells express molecular chaperones that suppress protein aggregation by inhibiting illicit protein protein interactions. We refer to this class of chaperones as passive molecular chaperones,' since they do not require an external energy source in order to function. We use simulations of a minimal model of passive chaperones and aggregation-prone client proteins to show how these chaperones increase the solubility of the proteome as a whole. This anti-aggregation mechanism is surprisingly effective, even when the chaperones are expressed in very low concentrations. Most importantly, we predict that passive chaperones that are optimized to stabilize the proteome while avoiding irreversible aggregation are likely to cluster in chaperone-only oligomers. This behavior is not functional per se-that is, it is not required for these chaperones to perform their anti-aggregation function-but nevertheless emerges as a side-effect of this optimization. Our analysis thus provides an explanation for an unusual behavior that is commonly observed in experiments on passive molecular chaperones.