Conformational diversity in the TPR domain-mediated interaction of protein phosphatase 5 with Hsp90

被引:69
作者
Cliff, MJ
Harris, R
Barford, D
Ladbury, JE
Williams, MA
机构
[1] UCL, Dept Biochem & Mol Biol, London WC1E 6BT, England
[2] Inst Canc Res, Chester Beatty Res Labs, Sect Struct Biol, London SW3 6JB, England
基金
英国医学研究理事会;
关键词
D O I
10.1016/j.str.2005.12.009
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Protein phosphatase 5 (Ppp5) is one of several proteins that bind to the Hsp90 chaperone via a tetratricopeptide repeat (TPR) domain. We report the solution structure of a complex of the TPR domain of Ppp5 with the C-terminal pentapeptide of Hsp90. This structure has the "two-carboxylate clamp" mechanism of peptide binding first seen in the Hop-TPR domain complexes with Hsp90 and Hsp70 peptides. However, NMR data reveal that the Ppp5 clamp is highly dynamic, and that there are multiple modes of peptide binding and mobility throughout the complex. Although this interaction is of very high affinity, relatively few persistent contacts are found between the peptide and the Ppp5-TPR domain, thus explaining its promiscuity in binding both Hsp70 and Hsp90 in vivo. We consider the possible implications of this dynamic structure for the mechanism of relief of auto-inhibition in Ppp5 and for the mechanisms of TPR-mediated recognition of Hsp90 by other proteins.
引用
收藏
页码:415 / 426
页数:12
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