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

  • Hugo Muñoz-Hernández
  • Mohinder Pal
  • Carlos F. Rodríguez
  • Chrisostomos Prodromou
  • Laurence H. Pearl
  • Oscar LlorcaEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1106)


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.


R2TP Prefoldin HSP90 Co-chaperone cryo-EM PIH1D1 RPAP3 RUVBL1 RUVBL2 TTT TELO2-TTI1-TTI2 complex Pih1 Tah1 Rvb1 Rvb2 



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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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Hugo Muñoz-Hernández
    • 1
  • Mohinder Pal
    • 2
  • Carlos F. Rodríguez
    • 1
  • Chrisostomos Prodromou
    • 2
  • Laurence H. Pearl
    • 2
  • Oscar Llorca
    • 1
    Email author
  1. 1.Spanish National Cancer Research Centre (CNIO)MadridSpain
  2. 2.Genome Damage and Stability Centre, School of Life SciencesUniversity of SussexBrightonUK

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