The function of small heat-shock proteins and their implication in proteostasis

Abstract

All organisms rely on a conserved cellular machinery supporting and controlling the life cycle of proteins: the proteostasis network. Within this network, the main players that determine the fate of proteins are molecular chaperones, the ubiquitin–proteasome and the lysosome–autophagy systems. sHsps (small heat-shock proteins) represent one family of molecular chaperones found in all domains of life. They prevent irreversible aggregation of unfolded proteins and maintain proteostasis by stabilizing promiscuously a variety of non-native proteins in an ATP-independent manner. In the cellular chaperone network, sHsps act as the first line of defence and keep their substrates in a folding-competent state until they are refolded by downstream ATP-dependent chaperone systems. Besides this interaction with unfolding substrates upon stress, sHsps show a different mode of binding for specific clients which are also recognized under physiological conditions. In vertebrates, sHsps are especially needed to maintain the refractive index of the eye lens. Additionally, sHsps are linked to a broad variety of diseases such as myopathies and neuropathies. The most striking feature of sHsps is their ability to form dynamic ensembles of higher oligomers. The activity of sHsps is regulated by changes in the composition of the ensembles.