Multiple molecular architectures of the eye lens chaperone ?B-crystallin elucidated by a triple hybrid approach.

ABSTRACT: The molecular chaperone ?B-crystallin, the major player in maintaining the transparency of the eye lens, prevents stress-damaged and aging lens proteins from aggregation. In nonlenticular cells, it is involved in various neurological diseases, diabetes, and cancer. Given its structural plasticity and dynamics, structure analysis of ?B-crystallin presented hitherto a formidable challenge. Here we present a pseudoatomic model of a 24-meric ?B-crystallin assembly obtained by a triple hybrid approach combining data from cryoelectron microscopy, NMR spectroscopy, and structural modeling. The model, confirmed by cross-linking and mass spectrometry, shows that the subunits interact within the oligomer in different, defined conformations. We further present the molecular architectures of additional well-defined ?B-crystallin assemblies with larger or smaller numbers of subunits, provide the mechanism how "heterogeneity" is achieved by a small set of defined structural variations, and analyze the factors modulating the oligomer equilibrium of ?B-crystallin and thus its chaperone activity.

SUBMITTER: Braun N 

PROVIDER: S-EPMC3251151 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature