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

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• HSP90 and the R2TP/Prefoldin-like (R2TP/PFDL) co-chaperone are essential for cellular stability, macromolecular complex assembly, and activation.
• Key cellular machinery, including RNA polymerase II, snoRNPs, and PI3-kinase-like kinases (e.g., ATM, ATR, mTOR), rely on the HSP90-R2TP system.
• The R2TP/PFDL pathway's role in cancer is linked to its involvement in frequently deregulated cancer pathways.

Purpose of the Study:

• To summarize recent structural findings on the R2TP co-chaperone.
• To elucidate the mechanistic insights into how R2TP/PFDL facilitates the assembly and activation of diverse macromolecular complexes.
• To understand the architecture of the R2TP core complex using cryo-electron microscopy (cryo-EM).

Main Methods:

• Cryo-electron microscopy (cryo-EM) for structural characterization of the R2TP core complex.
• Comparative structural analysis of yeast and human R2TP complexes.
• Review of recent structural findings related to R2TP/PFDL function.

Main Results:

• Recent structural studies are providing mechanistic insights into R2TP/PFDL function.
• Cryo-EM has significantly advanced the understanding of the R2TP core complex architecture.
• Structural differences between yeast and human R2TP highlight the complexity of metazoan R2TP.

Conclusions:

• The R2TP co-chaperone is central to recruiting HSP90 and its clients.
• Structural insights are beginning to explain how R2TP/PFDL facilitates assembly and activation of macromolecular complexes.
• Unanticipated complexities in metazoan R2TP raise new questions about its function in cellular processes.