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Advances on the Structure of the R2TP/Prefoldin-like Complex

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Prefoldins: the new chaperones

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1106))

Abstract

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.

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Acknowledgements

This work was supported by the Project EXCELENCIA SAF2017-82632-P, MCIU-AEI and cofounded by the European Regional Development fund (ERDF-EU) to OL and BES-2015-071348 to CFR. We thank Lidia Cerdán (CNB-CSIC) for help in Fig. 5.4.

Competing Financial Interests

The authors declare no competing financial interests.

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Author notes

  1. Authors Hugo Muñoz-Hernández, Mohinder Pal and Carlos F. Rodríguez have been equally contributed to this chapter.

Authors and Affiliations

  1. Spanish National Cancer Research Centre (CNIO), Madrid, Spain

    Hugo Muñoz-Hernández, Carlos F. Rodríguez & Oscar Llorca

  2. Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, UK

    Mohinder Pal, Chrisostomos Prodromou & Laurence H. Pearl

Authors
  1. Hugo Muñoz-Hernández
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  2. Mohinder Pal
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  3. Carlos F. Rodríguez
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  4. Chrisostomos Prodromou
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  5. Laurence H. Pearl
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  6. Oscar Llorca
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Corresponding author

Correspondence to Oscar Llorca .

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Editors and Affiliations

  1. Centro Nacional de Investigaciones Oncológicas, CNIO, Madrid, Spain

    Nabil Djouder

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Muñoz-Hernández, H., Pal, M., Rodríguez, C.F., Prodromou, C., Pearl, L.H., Llorca, O. (2018). Advances on the Structure of the R2TP/Prefoldin-like Complex. In: Djouder, N. (eds) Prefoldins: the new chaperones. Advances in Experimental Medicine and Biology, vol 1106. Springer, Cham. https://doi.org/10.1007/978-3-030-00737-9_5

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