RPAP3 provides a flexible scaffold for coupling HSP90 to the human R2TP co-chaperone complex

• DOI: 10.1038/s41467-018-03942-1
• Publication Date: 2018-04-10T16:28:42Z
• Authors: Fabrizio Martino; Mohinder Pal; Hugo Muñoz-Hernández; Carlos F. Rodríguez; Rafael Núñez-Ramírez; David Gil-Carton; Gianluca Degliesp...; J. Mark Skehel; S. Mark Roe; Chrisostomos Prod...; Laurence H. Pearl; Oscar Llorca
• Keywords: Chaperone (clinical)

The R2TP/Prefoldin-like co-chaperone, in concert with HSP90, facilitates assembly and cellular stability of RNA polymerase II, complexes PI3-kinase-like kinases such as mTOR. However, the mechanism by which this occurs is poorly understood. Here we use cryo-EM biochemical studies on human R2TP core (RUVBL1-RUVBL2-RPAP3-PIH1D1) reveal distinctive role RPAP3, distinguishing metazoan from smaller yeast equivalent. RPAP3 spans both faces a single RUVBL ring, providing an extended scaffold that recruits clients provides flexible tether for HSP90. A 3.6 Å structure reveals direct interaction C-terminal domain ATPase RUVBL2, necessary but absent yeast. mobile TPR domains map to opposite face associating PIH1D1, mediates client protein recruitment. Thus, platform bringing HSP90 into proximity diverse proteins.