Small Heat-Shock Proteins: Paramedics of the Cell

Abstract

The small heat-shock proteins (sHSPs) comprise a family of molecular chaperones which are widespread but poorly understood. Despite considerable effort, comparatively few high-resolution structures have been determined for the sHSPs, a likely consequence of their tendency to populate ensembles of inter-converting conformational and oligomeric states at equilibrium. This dynamic structure appears to underpin the sHSPs' ability to bind and sequester target proteins rapidly, and renders them the first line of defence against protein aggregation during disease and cellular stress. Here we describe recent studies on the sHSPs, with a particular focus on those which have provided insight into the structure and dynamics of these proteins. The combined literature reveals a picture of a remarkable family of molecular chaperones whose thermodynamic and kinetic properties are exquisitely balanced to allow functional regulation by subtle changes in cellular conditions.

Characterization of rice small heat shock proteins targeted to different cellular organelles

“…An arginine residue in the ACD which is conserved in sHSPs across all phyla was present in all rice sHSPs studied (van den et al 1999). We also identified the C-terminal IXI motifs which mediate higher-order oligomerization and access to substrate-binding regions, through conserved interactions with the ACD (Hilton et al 2013). …”

“…Small heat shock proteins (sHSPs) are a ubiquitous family of ATP-independent chaperones that constitute the first line of defence against the detrimental effects of cellular stress conditions (Hilton et al 2013). These proteins typically have monomeric masses between 12 and 40 kDa.…”

Structure and properties of chimeric small heat shock proteins containing yellow fluorescent protein attached to their C-terminal ends

“…Small heat shock proteins (sHsp) form a large family of ubiquitously expressed proteins having important housekeeping roles in the cell (Basha et al 2012;Hilton et al 2012;Mymrikov et al 2011). These proteins participate in regulation of the redox state of the cell and cytoskeleton, in proliferation and apoptosis, as well as in proteostasis that prevents aggregation of improperly folded proteins (Arrigo 2007;Ciocca et al 2013;Boncoraglio et al 2012).…”

“…The α-crystallin domain seems to be responsible for the formation of stable dimers of sHsp (Clark et al 2012). This domain is flanked by variable N-terminal and C-terminal regions that have important roles in the interaction of sHsp with protein targets, as well as in the formation of sHsp oligomers (Hilton et al 2012;Delbecq et al 2012). As a rule, sHsp form homooligomers or heterooligomers with a very flexible structure (Hilton et al 2012;Mymrikov et al 2012;Arrigo 2013).…”

“…This domain is flanked by variable N-terminal and C-terminal regions that have important roles in the interaction of sHsp with protein targets, as well as in the formation of sHsp oligomers (Hilton et al 2012;Delbecq et al 2012). As a rule, sHsp form homooligomers or heterooligomers with a very flexible structure (Hilton et al 2012;Mymrikov et al 2012;Arrigo 2013). These oligomers can undergo rapid association and dissociation by exchanging their subunits and can change their intracellular location upon different stimuli (Bryantsev et al 2002;Clarke and Mearow 2013).…”