title: Multiple molecular architectures of the eye lens chaperone αB-crystallin elucidated by a triple hybrid approach.
abstract: 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.
authors.affiliation: Center for Integrated Protein Science Munich, Chemistry Department, Technische Universität München, Lichtenbergstrasse 4, 85747 Garching, Germany.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Braun
authors.forename: Martin
authors.initials: M
authors.lastname: Zacharias
authors.forename: Jirka
authors.initials: J
authors.lastname: Peschek
authors.forename: Andreas
authors.initials: A
authors.lastname: Kastenmüller
authors.forename: Juan
authors.initials: J
authors.lastname: Zou
authors.forename: Marianne
authors.initials: M
authors.lastname: Hanzlik
authors.forename: Martin
authors.initials: M
authors.lastname: Haslbeck
authors.forename: Juri
authors.initials: J
authors.lastname: Rappsilber
authors.forename: Johannes
authors.initials: J
authors.lastname: Buchner
authors.forename: Sevil
authors.initials: S
authors.lastname: Weinkauf
mesh_terms: D003432:Cross-Linking Reagents / Q000737:chemistry; D020285:Cryoelectron Microscopy / Q000379:methods; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D021621:Imaging, Three-Dimensional / Q000379:methods; D007908:Lens, Crystalline / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D008854:Microscopy, Electron / Q000379:methods; D008958:Models, Molecular; D008968:Molecular Conformation; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D038203:alpha-Crystallin B Chain / Q000737:chemistry*
chemical_list: D003432:Cross-Linking Reagents; D006360:Heat-Shock Proteins; D038203:alpha-Crystallin B Chain