Munoz-Pal-Rodriguez_etal_22june2018.pdf (10.49 MB)
Advances on the structure of the R2TP/Prefoldin-like complex
chapter
posted on 2023-06-09, 16:15 authored by Hugo Muñoz-Hernández, Mohinder Pal, Carlos F Rodríguez, Chrisostomos ProdromouChrisostomos Prodromou, Laurence PearlLaurence Pearl, Oscar LllorcaCellular 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 chaperonesPublisher
SpringerExternal DOI
Volume
1106Page range
73-83Pages
135.0Book title
PrefoldinsL the new chaperonesPlace of publication
ChamISBN
9783030007362Series
Advances in Experimental Medicine and BiologyDepartment affiliated with
- Biochemistry Publications
Research groups affiliated with
- Genome Damage and Stability Centre Publications
Notes
ISSN 0065-2598Full text available
- Yes
Peer reviewed?
- Yes
Editors
Nabil DjouderLegacy Posted Date
2018-12-14First Open Access (FOA) Date
2020-11-28First Compliant Deposit (FCD) Date
2018-12-19Usage metrics
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