The Small Ones Matter—sHsps in the Bacterial Chaperone Network

Abstract

Small heat shock proteins (sHsps) are an evolutionarily conserved class of ATP-independent chaperones that form the first line of defence during proteotoxic stress. sHsps are defined not only by their relatively low molecular weight, but also by the presence of a conserved α-crystallin domain, which is flanked by less conserved, mostly unstructured, N- and C-terminal domains. sHsps form oligomers of different sizes which deoligomerize upon stress conditions into smaller active forms. Activated sHsps bind to aggregation-prone protein substrates to form assemblies that keep substrates from irreversible aggregation. Formation of these assemblies facilitates subsequent Hsp70 and Hsp100 chaperone-dependent disaggregation and substrate refolding into native species. This mini review discusses what is known about the role and place of bacterial sHsps in the chaperone network.

Molecular chaperone function of three small heat-shock proteins from a model probiotic species

“…Although bacterial sHSP have been thoroughly studied (Obuchowski and Liberek 2020;Obuchowski et al 2021), chiefly in model species such as E. coli (Piróg et al 2021), only a very few works have investigated the sHSP of probiotic microorganisms (Capozzi et al 2011b;Khaskheli et al 2015). The involvement of L. plantarum sHSP in stress response strategies was demonstrated previously, mainly by expression, gene knockout (KO) and phenotypic studies (Fiocco et al 2007;Capozzi et al 2011a;Arena et al 2019).…”

“…Some sHSP bind their clients stably, storing them for the disaggregating machineries, while others can associate only transiently with the substrate (de Miguel et al 2009 ). Both sHSP types contribute to protein homeostasis and enhance bacterial cell survival under stress (Obuchowski et al 2021 ). There are other examples of earlier investigated sHSP that are not effective in protecting heat-damaged substrates from insolubilisation (Basha et al 2010 ; Obuchowski et al 2019 ).…”

“…Their structure is characterised by a low molecular weight (12–43 kDa) and the presence of a central, highly conserved α-crystallin domain (approximatively 100 amino acids long), flanked by N- and C-terminal regions with more variable sequence and length. sHSP bind denaturing proteins, thereby preventing their irreversible aggregation and maintaining them in a native-like refolding-competent state, so that, upon release, sHSP-trapped substrates can recover their native conformation thanks to the ensuing recruitment of ATP-dependent chaperones (Carra et al 2019 ; Obuchowski et al 2021 ; Reinle et al 2022 ).…”

α-Crystallin Domains of Five Human Small Heat Shock Proteins (sHsps) Differ in Dimer Stabilities and Ability to Incorporate Themselves into Oligomers of Full-Length sHsps

“…Small heat shock proteins (sHsps) form a large family of ubiquitously expressed proteins. Researchers have detected these proteins in all phyla of life, including viruses, bacteria, plants and animals [ 1 , 2 , 3 , 4 ]. sHsps form the first line of defense against different proteotoxic stresses [ 5 ].…”

Self-regulatory function of bacterial small heat shock protein IbpA through mRNA binding is conferred by a conserved arginine

“…As molecular chaperones, sHsps are widely conserved in all kingdoms of life to protect cellular protein homeostasis (proteostasis) by binding with and then sequestering misfolded proteins in an ATP-independent manner, which is termed as a 'sequestrase' activity (4). Other chaperones, such as Hsp70 family, are required for later refolding or degradation to disassociate co-aggregates between sHsps and substrate proteins since sHsps are not refolding-active (1,2,4). sHsps assemble into dimers and large oligomers (1)(2)(3)(4).…”