title: The chaperone αB-crystallin uses different interfaces to capture an amorphous and an amyloid client.
abstract: Small heat-shock proteins, including αB-crystallin (αB), play an important part in protein homeostasis, because their ATP-independent chaperone activity inhibits uncontrolled protein aggregation. Mechanistic details of human αB, particularly in its client-bound state, have been elusive so far, owing to the high molecular weight and the heterogeneity of these complexes. Here we provide structural insights into this highly dynamic assembly and show, by using state-of-the-art NMR spectroscopy, that the αB complex is assembled from asymmetric building blocks. Interaction studies demonstrated that the fibril-forming Alzheimer's disease Aβ1-40 peptide preferentially binds to a hydrophobic edge of the central β-sandwich of αB. In contrast, the amorphously aggregating client lysozyme is captured by the partially disordered N-terminal domain of αB. We suggest that αB uses its inherent structural plasticity to expose distinct binding interfaces and thus interact with a wide range of structurally variable clients.
authors.affiliation: Munich Center for Integrated Protein Science at Department Chemie, Technische Universität München, Garching, Germany.|Solid-state NMR Spectroscopy, Leibniz-Institut für Molekulare Pharmakologie, Berlin-Buch, Germany.
authors.forename: Andi
authors.initials: A
authors.lastname: Mainz
authors.affiliation: Munich Center for Integrated Protein Science at Department Chemie, Technische Universität München, Garching, Germany.
authors.forename: Jirka
authors.initials: J
authors.lastname: Peschek
authors.affiliation: Munich Center for Integrated Protein Science at Department Chemie, Technische Universität München, Garching, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Stavropoulou
authors.affiliation: Munich Center for Integrated Protein Science at Department Chemie, Technische Universität München, Garching, Germany.
authors.forename: Katrin C
authors.initials: KC
authors.lastname: Back
authors.affiliation: Unité de Bioinformatique Structurale, Institut Pasteur, Paris, France.
authors.forename: Benjamin
authors.identifier: http://orcid.org/0000-0003-4014-9195
authors.initials: B
authors.lastname: Bardiaux
authors.affiliation: Munich Center for Integrated Protein Science at Department Chemie, Technische Universität München, Garching, Germany.
authors.forename: Sam
authors.initials: S
authors.lastname: Asami
authors.affiliation: Munich Center for Integrated Protein Science at Department Chemie, Technische Universität München, Garching, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Prade
authors.affiliation: Munich Center for Integrated Protein Science at Department Chemie, Technische Universität München, Garching, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Peters
authors.affiliation: Munich Center for Integrated Protein Science at Department Chemie, Technische Universität München, Garching, Germany.
authors.forename: Sevil
authors.initials: S
authors.lastname: Weinkauf
authors.affiliation: Munich Center for Integrated Protein Science at Department Chemie, Technische Universität München, Garching, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Buchner
authors.affiliation: Munich Center for Integrated Protein Science at Department Chemie, Technische Universität München, Garching, Germany.|Institute of Structural Biology, Helmholtz-Zentrum München, Neuherberg, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Reif
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D038203:alpha-Crystallin B Chain / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000682:Amyloid; D038203:alpha-Crystallin B Chain