The multifaceted nature of aB-crystallin

Abstract

In vivo, small heat-shock proteins (sHsps) are key players in maintaining a healthy proteome. aB-crystallin (aB-c) or HspB5 is one of the most widespread and populous of the ten human sHsps. Intracellularly, aB-c acts via its molecular chaperone action as the first line of defence in preventing target protein unfolding and aggregation under conditions of cellular stress. In this review, we explore how the structure of aB-c confers its function and interactions within its oligomeric self, with other sHsps, and with aggregation-prone target proteins. Firstly, the interaction between the two highly conserved regions of aB-c, the central a-crystallin domain and the C-terminal IXI motif and how this regulates aB-c chaperone activity are explored. Secondly, subunit exchange is rationalised as an integral structural and functional feature of aB-c. Thirdly, it is argued that monomeric aB-c may be its most chaperone-species active, but at the cost of increased hydrophobicity and instability. Fourthly, the reasons why hetero-oligomerisation of aB-c with other sHsps is important in regulating cellular proteostasis are examined. Finally, the interaction of aB-c with aggregation-prone, partially folded target proteins is discussed. Overall, this paper highlights the remarkably diverse capabilities of aB-c as a caretaker of the cell. Show more