Advances on the structure of the R2TP/Prefoldin-like complex

Muñoz-Hernández, Hugo, Pal, Mohinder, Rodríguez, Carlos F, Prodromou, Chrisostomos, Pearl, Laurence H and Lllorca, Oscar (2018) Advances on the structure of the R2TP/Prefoldin-like complex. In: Djouder, Nabil (ed.) PrefoldinsL the new chaperones. Advances in Experimental Medicine and Biology, 1106 . Springer, Cham, pp. 73-83. ISBN 9783030007362

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Cellular stability, assembly and activation of a growing list of macromolecular complexes require the action of HSP90 working in concert with the R2TP/Prefoldin-like (R2TP/PFDL) co-chaperone. RNA polymerase II, snoRNPs and complexes of PI3-kinase-like kinases, a family that includes the ATM, ATR, DNA-PKcs, TRAPP, SMG1 and mTOR proteins, are among the clients of the HSP90-R2TP system. Evidence links the R2TP/PFDL pathway with cancer, most likely because of the essential role in pathways commonly deregulated in cancer. R2TP forms the core of the co-cochaperone and orchestrates the recruitment of HSP90 and clients, whereas prefoldin and additional prefoldin-like proteins, including URI, associate with R2TP, but their function is still unclear. The mechanism by which R2TP/PFLD facilitates assembly and activation of such a variety of macromolecular complexes is poorly understood. Recent efforts in the structural characterization of R2TP have started to provide some mechanistic insights. We summarize recent structural findings, particularly how cryo-electron microscopy (cryo-EM) is contributing to our understanding of the architecture of the R2TP core complex. Structural differences discovered between yeast and human R2TP reveal unanticipated complexities of the metazoan R2TP complex, and opens new and interesting questions about how R2TP/PFLD works.

Item Type: Book Section
Additional Information: ISSN 0065-2598
Keywords: R2TP; Prefoldin; HSP90; Co-chaperone; cryo-EM; PIH1D1; RPAP3; RUVBL1; RUVBL2; TTT; TELO2-TTI1-TTI2 complex; Pih1; Tah1; Rvb1; Rvb2;
Schools and Departments: School of Life Sciences > Biochemistry
Research Centres and Groups: Genome Damage and Stability Centre
Subjects: Q Science > Q Science (General)
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Depositing User: Chrisostomos Prodromou
Date Deposited: 14 Dec 2018 15:27
Last Modified: 28 Nov 2020 02:00

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