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Tah1 helix-swap dimerization prevents mixed Hsp90 co-chaperone complexes
journal contribution
posted on 2023-06-09, 00:01 authored by Rhodri M L Morgan, Mohinder Pal, S Mark Roe, Laurence PearlLaurence Pearl, Chrisostomos ProdromouChrisostomos ProdromouSpecific 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 a-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 a-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.
History
Publication status
- Published
File Version
- Published version
Journal
Acta Crystallographica Section D: Biological CrystallographyISSN
1399-0047Publisher
International Union of CrystallographyExternal DOI
Volume
D71Page range
1197-1206Department affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2016-01-15First Open Access (FOA) Date
2016-01-15First Compliant Deposit (FCD) Date
2016-01-15Usage metrics
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