Portal de Periódicos da CAPES

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

2011; National Academy of Sciences; Volume: 108; Issue: 51 Linguagem: Inglês

10.1073/pnas.1111014108

1091-6490

Nathalie Braun, Martin Zacharias, Jirka Peschek, Andreas Kastenmüller, Juan Zou, Marianne Hanzlik, Martin Haslbeck, Juri Rappsilber, Johannes Büchner, Sevil Weinkauf,

Yersinia bacterium, plague, ectoparasites research

The molecular chaperone αB-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 αB-crystallin presented hitherto a formidable challenge. Here we present a pseudoatomic model of a 24-meric αB-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 αB-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 αB-crystallin and thus its chaperone activity.