ジャーナル: Proc Natl Acad Sci U S A / 年: 2011 タイトル: Multiple molecular architectures of the eye lens chaperone αB-crystallin elucidated by a triple hybrid approach. 著者: Nathalie Braun / Martin Zacharias / Jirka Peschek / Andreas Kastenmüller / Juan Zou / Marianne Hanzlik / Martin Haslbeck / Juri Rappsilber / Johannes Buchner / Sevil Weinkauf / 要旨: 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 ...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.
PDB ID 2KLR was used for residues 69-150. Structure-elements for the remaining C- and N-termini were obtained by the found EM-Structure and structure prediction tools (fitted to the EM-Volume)
精密化
空間: REAL
得られたモデル
PDB-2ygd: Molecular architectures of the 24meric eye lens chaperone alphaB- crystallin elucidated by a triple hybrid approach