2026-07-21T14:57:26Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/65062024-11-29T20:17:00Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Martino, Fabrizio
author
Pal, Mohinder
author
Muñoz-Hernández, Hugo
author
Rodríguez, Carlos F
author
Núñez-Ramírez, Rafael
author
Gil-Carton, David
author
Degliesposti, Gianluca
author
Skehel, J Mark
author
Roe, S Mark
author
Prodromou, Chrisostomos
author
Pearl, Laurence H
author
Llorca Blanco, Oscar Antonio
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Ministerio de Economía y Competitividad (España)
funder
Wellcome Trust
2018-10-24T08:31:08Z
2018-10-24T08:31:08Z
2018-04-16
Nat Commun. 2018; 9(1): 1501.
10.1038/s41467-018-03942-1
2041-1723
2041-1723
Nature communications
29662061
http://hdl.handle.net/20.500.12105/6506
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.
eng
HUMAN TRANSCRIPTION MACHINERY
CHROMATIN-REMODELING COMPLEX
PROTEIN-INTERACTION NETWORK
RNA-POLYMERASE-II
COCHAPERONE COMPLEX
STRUCTURAL BASIS
TEL2
BINDING
TAH1
RESOLUTION
RPAP3 provides a flexible scaffold for coupling HSP90 to the human R2TP co-chaperone complex
journal article
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