6FO1

Human R2TP subcomplex containing 1 RUVBL1-RUVBL2 hexamer bound to 1 RBD domain from RPAP3.

Summary for 6FO1

• Entry DOI: 10.2210/pdb6fo1/pdb
• EMDB information: 4287
• Descriptor: RuvB-like 1, RuvB-like 2, RNA polymerase II-associated protein 3, ... (4 entities in total)
• Functional Keywords: r2tp, hsp90 co-chaperone, pih1d1, rpap3, ruvbl1-ruvbl2, chaperone
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 7
• Total formula weight: 382951.89

Authors

Martino, F.,Munoz-Hernandez, H.,Rodriguez, C.F.,Pearl, L.H.,Llorca, O. (deposition date: 2018-02-05, release date: 2018-04-04, Last modification date: 2019-12-11)

Primary citation

Martino, F.,Pal, M.,Munoz-Hernandez, H.,Rodriguez, C.F.,Nunez-Ramirez, R.,Gil-Carton, D.,Degliesposti, G.,Skehel, J.M.,Roe, S.M.,Prodromou, C.,Pearl, L.H.,Llorca, O.
RPAP3 provides a flexible scaffold for coupling HSP90 to the human R2TP co-chaperone complex.
Nat Commun, 9:1501-1501, 2018

PubMed Abstract: The R2TP/Prefoldin-like co-chaperone, in concert with HSP90, facilitates assembly and cellular stability of RNA polymerase II, and complexes of PI3-kinase-like kinases such as mTOR. However, the mechanism by which this occurs is poorly understood. Here we use cryo-EM and biochemical studies on the human R2TP core (RUVBL1-RUVBL2-RPAP3-PIH1D1) which reveal the distinctive role of RPAP3, distinguishing metazoan R2TP from the smaller yeast equivalent. RPAP3 spans both faces of a single RUVBL ring, providing an extended scaffold that recruits clients and provides a flexible tether for HSP90. A 3.6 Å cryo-EM structure reveals direct interaction of a C-terminal domain of RPAP3 and the ATPase domain of RUVBL2, necessary for human R2TP assembly but absent from yeast. The mobile TPR domains of RPAP3 map to the opposite face of the ring, associating with PIH1D1, which mediates client protein recruitment. Thus, RPAP3 provides a flexible platform for bringing HSP90 into proximity with diverse client proteins.

PubMed: 29662061
DOI: 10.1038/s41467-018-03942-1

Experimental method

ELECTRON MICROSCOPY (3.57 Å)