A Novel Quaternary Structure of the Dimeric α-Crystallin Domain with Chaperone-like Activity

Abstract

αB-crystallin, a member of the small heat-shock protein family and a major eye lens protein, is a high molecular mass assembly and can act as a molecular chaperone. We report a synchrotron radiation x-ray solution scattering study of a truncation mutant from the human αB-crystallin (αB57-157), a dimeric protein that comprises the α-crystallin domain of the αB-crystallin and retains a significant chaperone-like activity. According to the sequence analysis (more than 23% identity), the monomeric fold of the α-crystallin domain should be close to that of the small heat-shock protein from Methanococcusjannaschii (MjHSP16.5). The theoretical scattering pattern computed from the crystallographic model of the dimeric MjHSP16.5 deviates significantly from the experimental scattering by the α-crystallin domain, pointing to different quaternary structures of the two proteins. A rigid body modeling against the solution scattering data yields a model of the α-crystallin domain revealing a new dimerization interface. The latter consists of a strand-turn-strand motif contributed by each of the monomers, which form a four-stranded, antiparallel, intersubunit composite β-sheet. This model agrees with the recent spin labeling results and suggests that the αB-crystallin is composed by flexible building units with an extended surface area. This flexibility may be important for biological activity and for the formation of αB-crystallin complexes of variable sizes and compositions.