EM structure yeast.pdf (13.66 MB)
The structure of the R2TP complex defines a platform for recruiting diverse client proteins to the HSP90 molecular chaperone system
journal contribution
posted on 2023-06-09, 07:28 authored by Angel Rivera-Calzada, Mohinder Pal, Hugo Muñoz-Hernández, Juan R Luque-Ortega, David Gil-Carton, Gianluca Degliesposti, J. Mark Skehel, Chrisostomos ProdromouChrisostomos Prodromou, Laurence PearlLaurence Pearl, Oscar llorcaThe R2TP complex, comprising the Rvb1p-Rvb2p AAA-ATPases, Tah1p, and Pih1p in yeast, is a special- ized Hsp90 co-chaperone required for the assembly and maturation of multi-subunit complexes. These include the small nucleolar ribonucleoproteins, RNA polymerase II, and complexes containing phosphati- dylinositol-3-kinase-like kinases. The structure and stoichiometry of yeast R2TP and how it couples to Hsp90 are currently unknown. Here, we determine the 3D organization of yeast R2TP using sedimenta- tion velocity analysis and cryo-electron microscopy. The 359-kDa complex comprises one Rvb1p/Rvb2p hetero-hexamer with domains II (DIIs) forming an open basket that accommodates a single copy of Tah1p-Pih1p. Tah1p-Pih1p binding to multiple DII do- mains regulates Rvb1p/Rvb2p ATPase activity. Using domain dissection and cross-linking mass spectro- metry, we identified a unique region of Pih1p that is essential for interaction with Rvb1p/Rvb2p. These data provide a structural basis for understanding how R2TP couples an Hsp90 dimer to a diverse set of client proteins and complexes.
History
Publication status
- Published
File Version
- Published version
Journal
StructureISSN
0969-2126Publisher
ElsevierExternal DOI
Issue
7Volume
25Page range
1145-1152Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Research groups affiliated with
- Genome Damage and Stability Centre Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2017-07-28First Open Access (FOA) Date
2017-07-28First Compliant Deposit (FCD) Date
2017-07-27Usage metrics
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