4cgq
Full length Tah1 bound to HSP90 peptide SRMEEVD
Structural highlights
FunctionPublication Abstract from PubMedSpecific co-chaperone adaptors facilitate the recruitment of client proteins to the Hsp90 system. Tah1 binds the C-terminal conserved MEEVD motif of Hsp90, thus linking an eclectic set of client proteins to the R2TP complex for their assembly and regulation by Hsp90. Rather than the normal complement of seven alpha-helices seen in other tetratricopeptide repeat (TPR) domains, Tah1 unusually consists of the first five only. Consequently, the methionine of the MEEVD peptide remains exposed to solvent when bound by Tah1. In solution Tah1 appears to be predominantly monomeric, and recent structures have failed to explain how Tah1 appears to prevent the formation of mixed TPR domain-containing complexes such as Cpr6-(Hsp90)2-Tah1. To understand this further, the crystal structure of Tah1 in complex with the MEEVD peptide of Hsp90 was determined, which shows a helix swap involving the fifth alpha-helix between two adjacently bound Tah1 molecules. Dimerization of Tah1 restores the normal binding environment of the bound Hsp90 methionine residue by reconstituting a TPR binding site similar to that in seven-helix-containing TPR domain proteins. Dimerization also explains how other monomeric TPR-domain proteins are excluded from forming inappropriate mixed co-chaperone complexes. Tah1 helix-swap dimerization prevents mixed Hsp90 co-chaperone complexes.,Morgan RM, Pal M, Roe SM, Pearl LH, Prodromou C Acta Crystallogr D Biol Crystallogr. 2015 May;71(Pt 5):1197-206. doi:, 10.1107/S1399004715004551. Epub 2015 Apr 25. PMID:25945584[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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