Anti-aggregation activity of small heat shock proteins under crowded conditions

It is becoming evident that small heat shock proteins (sHsps) are important players of protein homeostasis system. Their ability to bind misfolded proteins may play a crucial role in preventing protein aggregation in cells. The remarkable structural plasticity of sHsps is considered to underlie the mechanism of their activity. However, all our knowledge of the anti-aggregation functioning of sHsps is based on data obtained in vitro in media greatly different from the cellular highly crowded milieu. The present review highlights available data on the effect of crowding on the anti-aggregation activity of sHsps. There is some evidence that crowding affects conformation and dynamics of sHsps oligomers as well as their anti-aggregation properties. Crowding stimulates association of sHsp-client protein complexes into large-sized aggregates thus diminishing the apparent anti-aggregation activity of sHsps. Nevertheless, it is also shown that complexes between suboligomers (dissociated forms) of sHsps and client proteins may be stabilized and exist for longer period of time under crowded conditions. Moreover, crowding may retard the initial stages of aggregation which correspond to the formation of sHsp-containing nuclei and their clusters. Thus, dissociation of sHsps into suboligomers appears to be an important feature for the anti-aggregation activity of sHsps in crowded media.