Structural and functional properties of proteins interacting with small heat shock proteins

Abstract

Small heat shock proteins (sHsps) are ubiquitous molecular chaperones found in all domains of life, possessing significant roles in protein quality control in cells and assisting the refolding of non-native proteins. They are efficient chaperones against many in vitro protein substrates. Nevertheless, the in vivo native substrates of sHsps are not known. To better understand the functions of sHsps and the mechanisms by which they enhance heat resistance, sHsp-interacting proteins were identified using affinity purification under heat shock conditions. This paper aims at providing some insights into the characteristics of natural substrate proteins of sHsps. It seems that sHsps of prokaryotes, as well as sHsps of some eukaryotes, can bind to a wide range of substrate proteins with a preference for certain functional classes of proteins. Using Drosophila melanogaster mitochondrial Hsp22 as a model system, we observed that this sHsp interacted with the members of ATP synthase machinery. Mechanistically, Hsp22 interacts with the multi-type substrate proteins under heat shock conditions as well as non-heat shock conditions.

Keywords: Drosophila melanogaster; Hsp22; Molecular chaperone; Protein substrates; Small heat shock protein (sHsp).

Fig. 1

Mechanism of chaperone function of sHsps. sHsps exist in a wide variety of oligomers with different sizes which exchange their subunits consequently (I). In response to stress, a large variety of substrates are destabilized and form partially unfolded substrate (II). This causes activation of sHsps through formation of a population which can capture early denatured substrates by their substrate-binding sites (III). The activated species bind to the large range of non-native substrate proteins which sometimes are integrated in the oligomeric structure and prevent them from undergoing irreversible aggregation by the formation of sHsps-substrate complexes (IV). Finally, the bound substrates can be released from the complexes and refolded with the help of the ATP-dependent Hsp70/40/NEF chaperone system (V)