2026-07-21T14:57:55Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/65062024-11-29T20:17:00Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc 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 author 2018-04-16 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. 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 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