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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 ?-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.

SUBMITTER: Park SJ

PROVIDER: S-EPMC3087862 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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The client protein p53 adopts a molten globule-like state in the presence of Hsp90.

Park Sung Jean SJ Borin Brendan N BN Martinez-Yamout Maria A MA Dyson H Jane HJ

Nature structural & molecular biology 20110403 5

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-she ...[more]

PMID: 21460846

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