The structure of the R2TP complex defines a platform for recruiting diverse client proteins to the HSP90 molecular chaperone system

Rivera-Calzada, Angel, Pal, Mohinder, Muñoz-Hernández, Hugo, Luque-Ortega, Juan R, Gil-Carton, David, Degliesposti, Gianluca, Skehel, J. Mark, Prodromou, Chrisostomos, Pearl, Laurence H and llorca, Oscar (2017) The structure of the R2TP complex defines a platform for recruiting diverse client proteins to the HSP90 molecular chaperone system. Structure, 25 (7). pp. 1145-1152. ISSN 0969-2126

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Abstract

The 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.

Item Type: Article
Keywords: Chaperone, Cochaperone, Hsp90, R2TP, Rvb1, RuvB2, Tah1, Pih1
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Research Centres and Groups: Genome Damage and Stability Centre
Subjects: Q Science > QD Chemistry > QD0241 Organic chemistry > QD0415 Biochemistry
Depositing User: Chrisostomos Prodromou
Date Deposited: 28 Jul 2017 08:30
Last Modified: 28 Jul 2017 08:39
URI: http://sro.sussex.ac.uk/id/eprint/69508

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