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

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posted on 2023-06-09, 16:15 authored by Hugo Muñoz-Hernández, Mohinder Pal, Carlos F Rodríguez, Chrisostomos ProdromouChrisostomos Prodromou, Laurence PearlLaurence Pearl, Oscar Lllorca
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.

History

Publication status

  • Published

File Version

  • Accepted version

Journal

Advances in Experimental Medicine and Biology: Prefoldins: the new chaperones

Publisher

Springer

Volume

1106

Page range

73-83

Pages

135.0

Book title

PrefoldinsL the new chaperones

Place of publication

Cham

ISBN

9783030007362

Series

Advances in Experimental Medicine and Biology

Department affiliated with

  • Biochemistry Publications

Research groups affiliated with

  • Genome Damage and Stability Centre Publications

Notes

ISSN 0065-2598

Full text available

  • Yes

Peer reviewed?

  • Yes

Editors

Nabil Djouder

Legacy Posted Date

2018-12-14

First Open Access (FOA) Date

2020-11-28

First Compliant Deposit (FCD) Date

2018-12-19

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