dc.contributor.author | Martino, Fabrizio | |
dc.contributor.author | Pal, Mohinder | |
dc.contributor.author | Muñoz-Hernández, Hugo | |
dc.contributor.author | Rodríguez, Carlos F | |
dc.contributor.author | Núñez-Ramírez, Rafael | |
dc.contributor.author | Gil-Carton, David | |
dc.contributor.author | Degliesposti, Gianluca | |
dc.contributor.author | Skehel, J Mark | |
dc.contributor.author | Roe, S Mark | |
dc.contributor.author | Prodromou, Chrisostomos | |
dc.contributor.author | Pearl, Laurence H | |
dc.contributor.author | Llorca Blanco, Oscar Antonio | |
dc.date.accessioned | 2018-10-24T08:31:08Z | |
dc.date.available | 2018-10-24T08:31:08Z | |
dc.date.issued | 2018-04-16 | |
dc.identifier.citation | Nat Commun. 2018; 9(1): 1501. | es_ES |
dc.identifier.issn | 2041-1723 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/6506 | |
dc.description.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. | es_ES |
dc.description.sponsorship | This 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.iso | eng | es_ES |
dc.publisher | Nature Publishing Group | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | HUMAN TRANSCRIPTION MACHINERY | es_ES |
dc.subject | CHROMATIN-REMODELING COMPLEX | es_ES |
dc.subject | PROTEIN-INTERACTION NETWORK | es_ES |
dc.subject | RNA-POLYMERASE-II | es_ES |
dc.subject | COCHAPERONE COMPLEX | es_ES |
dc.subject | STRUCTURAL BASIS | es_ES |
dc.subject | TEL2 | es_ES |
dc.subject | BINDING | es_ES |
dc.subject | TAH1 | es_ES |
dc.subject | RESOLUTION | es_ES |
dc.title | RPAP3 provides a flexible scaffold for coupling HSP90 to the human R2TP co-chaperone complex | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 29662061 | es_ES |
dc.format.volume | 9 | es_ES |
dc.format.number | 1 | es_ES |
dc.format.page | 1501 | es_ES |
dc.identifier.doi | 10.1038/s41467-018-03942-1 | es_ES |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Wellcome Trust | |
dc.description.peerreviewed | Sí | |
dc.identifier.e-issn | 2041-1723 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1038/s41467- 018-03942-1 | es_ES |
dc.identifier.journal | Nature communications | es_ES |
dc.repisalud.institucion | CNIO | es_ES |
dc.repisalud.orgCNIO | CNIO::Grupos de investigación | es_ES |
dc.repisalud.orgCNIO | CNIO::Grupos de investigación::Grupo de Complejos Macromoleculares en la Respuesta a Daños en el DNA | es_ES |
dc.rights.accessRights | open access | es_ES |