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dc.contributor.authorMartino, Fabrizio
dc.contributor.authorPal, Mohinder
dc.contributor.authorMuñoz-Hernández, Hugo
dc.contributor.authorRodríguez, Carlos F
dc.contributor.authorNúñez-Ramírez, Rafael
dc.contributor.authorGil-Carton, David
dc.contributor.authorDegliesposti, Gianluca
dc.contributor.authorSkehel, J Mark
dc.contributor.authorRoe, S Mark
dc.contributor.authorProdromou, Chrisostomos
dc.contributor.authorPearl, Laurence H
dc.contributor.authorLlorca Blanco, Oscar Antonio 
dc.date.accessioned2018-10-24T08:31:08Z
dc.date.available2018-10-24T08:31:08Z
dc.date.issued2018-04-16
dc.identifier.citationNat Commun. 2018; 9(1): 1501.es_ES
dc.identifier.issn2041-1723es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6506
dc.description.abstractThe 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.es_ES
dc.description.sponsorshipThis work was supported by the Spanish Ministry of Economy, Industry and Competitiveness and the "Agencia Estatal de Investigación" (MINECO/AEI), co-funded by the European Regional Development Fund (ERDF) (SAF2014-52301-R and SAF2017- 82632-P to O.L., SAF2014-59993-JIN to F.M., and BES-2015-071348 to C.F.R.), the Spanish National Research Council (i-LINK0997 to O.L.), a Wellcome Trust Senior Investigator award (095605/Z/11/Z), and Award Enhancement Grant (095605/Z/11/A) (to L.H.P.). We acknowledge Diamond for access and support of the Cryo-EM facilities at the UK national electron bio-imaging centre (eBIC), proposals EM13312, EM13520, and EM15997, funded by the Wellcome Trust, MRC and BBSRC. Preliminary work used the platforms of the Grenoble Instruct-ERIC Center (ISBG: UMS 3518 CNRS-CEA-UGA- EMBL) with support from FRISBI (ANR-10-INSB-05-02) and GRAL (ANR-10-LABX-49- 01) within the Grenoble Partnership for Structural Biology (PSB). The electron micro- scope facility is supported by the Rhône-Alpes Region, the Fondation Recherche Medicale (FRM), the funds FEDER, the CEA, and the GIS-Infrastrutures en Biologie Sante et Agronomie (IBISA). We also acknowledge the help of Guy Schoehn (IBS-Grenoble). INSTRUCT and iNEXT supported access to the cryo-EM facilities. We thank the EM Units of the CIB-CSIC and the CNIO for support in preparing and screening the grids.es_ES
dc.language.isoenges_ES
dc.publisherNature Publishing Group es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectHUMAN TRANSCRIPTION MACHINERYes_ES
dc.subjectCHROMATIN-REMODELING COMPLEXes_ES
dc.subjectPROTEIN-INTERACTION NETWORKes_ES
dc.subjectRNA-POLYMERASE-IIes_ES
dc.subjectCOCHAPERONE COMPLEXes_ES
dc.subjectSTRUCTURAL BASISes_ES
dc.subjectTEL2es_ES
dc.subjectBINDINGes_ES
dc.subjectTAH1es_ES
dc.subjectRESOLUTIONes_ES
dc.titleRPAP3 provides a flexible scaffold for coupling HSP90 to the human R2TP co-chaperone complexes_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID29662061es_ES
dc.format.volume9es_ES
dc.format.number1es_ES
dc.format.page1501es_ES
dc.identifier.doi10.1038/s41467-018-03942-1es_ES
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderWellcome Trust 
dc.description.peerreviewed
dc.identifier.e-issn2041-1723es_ES
dc.relation.publisherversionhttps://doi.org/10.1038/s41467- 018-03942-1es_ES
dc.identifier.journalNature communicationses_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigaciónes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Complejos Macromoleculares en la Respuesta a Daños en el DNAes_ES
dc.rights.accessRightsopen accesses_ES


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