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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2004-3-24
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pubmed:abstractText |
Hsp90 is a molecular chaperone essential for the activation and assembly of many key eukaryotic signalling and regulatory proteins. Hsp90 is assisted and regulated by co-chaperones that participate in an ordered series of dynamic multiprotein complexes, linked to Hsp90 conformationally coupled ATPase cycle. The co-chaperones Aha1 and Hch1 bind to Hsp90 and stimulate its ATPase activity. Biochemical analysis shows that this activity is dependent on the N-terminal domain of Aha1, which interacts with the central segment of Hsp90. The structural basis for this interaction is revealed by the crystal structure of the N-terminal domain (1-153) of Aha1 (equivalent to the whole of Hch1) in complex with the middle segment of Hsp90 (273-530). Structural analysis and mutagenesis show that binding of N-Aha1 promotes a conformational switch in the middle-segment catalytic loop (370-390) of Hsp90 that releases the catalytic Arg 380 and enables its interaction with ATP in the N-terminal nucleotide-binding domain of the chaperone.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0261-4189
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1402-10
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15039704-Adenosine Triphosphatases,
pubmed-meshheading:15039704-Amino Acid Sequence,
pubmed-meshheading:15039704-Binding Sites,
pubmed-meshheading:15039704-Catalysis,
pubmed-meshheading:15039704-Chaperonins,
pubmed-meshheading:15039704-Genes, Suppressor,
pubmed-meshheading:15039704-HSP90 Heat-Shock Proteins,
pubmed-meshheading:15039704-Models, Molecular,
pubmed-meshheading:15039704-Molecular Chaperones,
pubmed-meshheading:15039704-Molecular Sequence Data,
pubmed-meshheading:15039704-Protein Binding,
pubmed-meshheading:15039704-Protein Structure, Secondary,
pubmed-meshheading:15039704-Protein Structure, Tertiary,
pubmed-meshheading:15039704-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:15039704-Sequence Alignment,
pubmed-meshheading:15039704-Structure-Activity Relationship
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pubmed:year |
2004
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pubmed:articleTitle |
Structural basis for recruitment of the ATPase activator Aha1 to the Hsp90 chaperone machinery.
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pubmed:affiliation |
Chester Beatty Laboratories, Section of Structural Biology, The Institute of Cancer Research, London, UK.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Corrected and Republished Article,
Research Support, N.I.H., Extramural
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