Abstract
Small heat shock proteins (sHsps) are a conserved class of ATP-independent chaperones that bind to aggregation-prone polypeptides at stress conditions. sHsps encage these polypeptides in assemblies, shielding them from further aggregation. To facilitate their subsequent solubilization and refolding by Hsp70 (DnaK) and Hsp100 (ClpB) chaperones, first, sHsps need to dissociate from the assemblies. In most γ-proteobacteria, these functions are fulfilled by a single sHsp (IbpA), but in a subset of Enterobacterales, a two-protein sHsp (IbpA and IbpB) system has evolved. To gain insight into the emergence of complexity within this chaperone system, we reconstructed the phylogeny of γ-proteobacteria and their sHsps. We selected proteins representative of systems comprising either one or two sHsps and analysed their ability to form sHsps-substrate assemblies. All the tested IbpA proteins, but not IbpBs, stably interact with an aggregating substrate. Moreover, in Escherichia coli cells, ibpA but not ibpB suppress the growth defect associated with low DnaK level, which points to the major protective role of IbpA during the breakdown of protein quality control. We also examined how sHsps affect the association of Hsp70 with the assemblies at the initial phase of disaggregation and how they affect protein recovery after stress. Our results suggest that a single gene duplication event has given rise to the sHsp system consisting of a strong canonical binder, IbpA, and its non-canonical paralog IbpB that enhances sHsps dissociation from the assemblies. The cooperation between the sHsps reduces the demand for Hsp70 needed to outcompete them from the assemblies by promoting sHsps dissociation without compromising assembly formation at heat shock. This potentially increases the robustness and elasticity of sHsps protection against irreversible aggregation.
Highlights
When a cell is exposed to heat shock, intracellular proteins aggregate, which results in the imbalance of protein homeostasis [1, 2]
Our results indicate that after a gene duplication event, one small heat shock proteins (sHsps) specialized in tight substrate binding, whereas another sHsp became important for efficient dissociation of both sHsps to enable recovery of proteins trapped in the assemblies
To gain insight into how the bacterial protein quality control system has been enriched with another small heat shock protein, we carried out evolutionary analysis of y-proteobacteria and their sHsps
Summary
When a cell is exposed to heat shock, intracellular proteins aggregate, which results in the imbalance of protein homeostasis (proteostasis) [1, 2]. The presence of the protein quality control network restores the proteostasis by counteracting misfolding and by processing aggregated polypeptides [1, 3]. These polypeptides are either degraded by cellular proteases or disaggregated by a chaperone system consisting of three major components. This system includes small heat shock proteins (sHsps), the Hsp chaperone system (DnaK with DnaJ and GrpE cochaperones) and an Hsp100 disaggregase (ClpB) [4, 5]. The assemblies are recognized by Hsp70 [10, 11] and further processed by both Hsp and Hsp100, which leads to extraction of single polypeptides from aggregates and their subsequent refolding [11, 12]
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