Disruption of a conserved N-terminal IXI motif of αB-crystallin leads to the formation of dynamic fibrillar aggregates

Abstract

Proteostasis of the human eye lens is supported by a pair of small heat shock proteins (sHSPs), known as α-crystallins ( αA- and αB-isoforms). These proteins function as polydisperse multimers that sequester destabilized proteins and prevent them from aggregating in an ATP-independent manner (aka a “holdase”). In the eye lens, these features are thought to prevent the formation of light-scattering aggregates that give rise to age-related cataract. The functional polydispersity and chaperone function of the α-crystallins are mediated by intrinsically disordered regions located at the protein’s n-terminal domain (NTD) and c-terminal extension (CTE).