Preferential and specific binding of human ?B-crystallin to a cataract-related variant of ?S-crystallin.

ABSTRACT: Transparency in the eye lens is maintained via specific, functional interactions among the structural ??- and chaperone ?-crystallins. Here, we report the structure and ?-crystallin binding interface of the G18V variant of human ?S-crystallin (?S-G18V), which is linked to hereditary childhood-onset cortical cataract. Comparison of the solution nuclear magnetic resonance structures of wild-type and G18V ?S-crystallin, both presented here, reveal that the increased aggregation propensity of ?S-G18V results from neither global misfolding nor the solvent exposure of a hydrophobic residue but instead involves backbone rearrangement within the N-terminal domain. ?B-crystallin binds more strongly to the variant, via a well-defined interaction surface observed via chemical shift differences. In the context of the ?B-crystallin structure and the finding that it forms heterogeneous multimers, our structural studies suggest a potential mechanism for cataract formation via the depletion of the finite ?B-crystallin population of the lens.

SUBMITTER: Kingsley CN 

PROVIDER: S-EPMC3940334 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature