title: The client protein p53 adopts a molten globule-like state in the presence of Hsp90.
abstract: It is not currently known in what state (folded, unfolded or alternatively folded) client proteins interact with the chaperone Hsp90. We show that one client, the p53 DNA-binding domain, undergoes a structural change in the presence of Hsp90 to adopt a molten globule-like state. Addition of one- and two-domain constructs of Hsp90, as well as the full-length three-domain protein, to isotopically labeled p53 led to reduction in NMR signal intensity throughout p53, particularly in its central β-sheet. This reduction seems to be associated with a change of structure of p53 without formation of a distinct complex with Hsp90. Fluorescence and hydrogen-exchange measurements support a loosening of the structure of p53 in the presence of Hsp90 and its domains. We propose that Hsp90 interacts with p53 by multiple transient interactions, forming a dynamic heterogeneous manifold of conformational states that resembles a molten globule.
authors: Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
authors: Sung Jean
authors: SJ
authors: Park
authors: Brendan N
authors: BN
authors: Borin
authors: Maria A
authors: MA
authors: Martinez-Yamout
authors: H Jane
authors: HJ
authors: Dyson
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013050:Spectrometry, Fluorescence; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000378:metabolism
chemical_list: D018841:HSP90 Heat-Shock Proteins; D016159:Tumor Suppressor Protein p53