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

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.

• Publication year

  2011

• Venue

  Nature Structural &Molecular Biology

• Publication date

  2011-01-27

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1038/nsmb.2045PMID 21460846PMCID 3087862
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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