Document Detail


Localization of sites of interaction between p23 and Hsp90 in solution.
MedLine Citation:
PMID:  16565516     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The co-chaperone p23 forms a complex with the chaperone Hsp90 that mediates the folding pathway leading to the production of functional steroid receptors. Solution NMR spectroscopy has been used to characterize sites of interaction between Hsp90 and p23. Titration of p23 with Hsp90 results in the selective broadening of certain cross-peaks in the 15N-1H heteronuclear single quantum correlation (HSQC) spectrum. The interaction sites on p23 and Hsp90 have been localized by dissection of Hsp90 into single-domain and two-domain constructs. The N-terminal (N) domain of Hsp90 does not affect the NMR spectrum of p23 either in the presence or absence of the ATP analogue ATPgammaS. Similarly, the HSQC spectrum of 15N-labeled N domain is unperturbed by the addition of p23. A subset of cross-peaks in the HSQC spectrum of p23 is shifted upon addition of the middle (M) domain of Hsp90, and the same shifts are observed upon the addition of the two-domain construct containing the N and M domains (NM). The addition of the co-chaperone Aha1, which is known to bind to the M domain of Hsp90, displaces p23 from Hsp90. The resonances that shift upon addition of the M and NM Hsp90 constructs correspond to those that were broadened at the lowest ratios of full-length Hsp90 to p23 and define an Hsp90 binding site that includes much of the C-terminal sequence of p23 together with a contiguous beta-hairpin from the N terminus. We conclude that p23 forms a specific complex with Hsp90 primarily through binding to its middle domain.
Authors:
Maria A Martinez-Yamout; Rani P Venkitakrishnan; Nicholas E Preece; Gerard Kroon; Peter E Wright; H Jane Dyson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-03-25
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  281     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-05-15     Completed Date:  2006-07-21     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  14457-64     Citation Subset:  IM    
Affiliation:
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Binding Sites
Circular Dichroism
HSP90 Heat-Shock Proteins / chemistry*
Humans
Intramolecular Oxidoreductases
Liver / metabolism
Magnetic Resonance Spectroscopy
Models, Molecular
Molecular Chaperones / physiology*
Phosphoproteins / physiology*
Protein Binding
Protein Structure, Tertiary
Grant Support
ID/Acronym/Agency:
GM57374/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/HSP90 Heat-Shock Proteins; 0/Molecular Chaperones; 0/Phosphoproteins; EC 5.3.-/Intramolecular Oxidoreductases; EC 5.3.99.3/prostaglandin-E synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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