Lens α-crystallin: Function and structure

Abstract

α-Crystallin is a major lens protein, comprising up to 40% of total lens proteins, where its structural function is to assist in maintaining the proper refractive index in the lens. In addition to its structural role, it has been shown to function in a chaperone-like manner. The chaperone-like function of α-crystallin will help prevent the formation of large light-scattering aggregates and possibly cataract. In the lens, α-crystallin is a polydisperse molecule consisting of a 3:1 ratio of αA to αB subunits. In this study, we expressed recombinant αA- and αB-crystallin in E. coli and compared the polydispersity, structure and aggregation state between each other and native bovine lens α-crystallin. Using gel permeation chromatography to assay for polydispersity, we found native α-crystallin to be significantly more polydisperse than either recombinant αA- or αB-crystallin, with αB-crystallin having the most homogeneous structure of the three. Reconstructed images of αB-crystallin obtained with cryo-electron microscopy support the concept that αB-crystallin is an extremely dynamic molecule and demonstrated that it has a hollow interior. Interestingly, we present evidence that native α-crystallin is significantly more thermally stable than either αA- or αB-crystallin alone. In fact, our experiments suggest that a 3:1 ratio of αA to αB subunit composition in an α-crystallin molecule is optimal in terms of thermal stability. This fascinating result explains the stoichiometric ratios of αA- and αB-crystallin subunits in the mammalian lens.