The role of Hsp90 in protein complex assembly

Abstract

Hsp90 is a ubiquitous and essential molecular chaperone that plays central roles in many signaling and other cellular pathways. The in vivo and in vitro activity of Hsp90 depends on its association with a wide variety of cochaperones and cofactors, which form large multi-protein complexes involved in folding client proteins. Based on our proteomic work mapping the molecular chaperone interaction networks in yeast, especially that of Hsp90, as well as, on experiments and results presented in the published literature, one major role of Hsp90 appears to be the promotion and maintenance of proper assembly of protein complexes. To highlight this role of Hsp90, the effect of the chaperone on the assembly of the following seven complexes is discussed in this review: snoRNP, RNA polymerase II, phosphatidylinositol-3 kinase-related protein kinase (PIKK), telomere complex, kinetochore, RNA induced silencing complexes (RISC), and 26S proteasome. For some complexes, it is observed that Hsp90 mediates complex assembly by stabilizing an unstable protein subunit and facilitating its incorporation into the complex; for other complexes, Hsp90 promotes change in the composition of that complex. In all cases, Hsp90 does not appear to be part of the final assembled complex. This article is part of a Special Issue entitled:Heat Shock Protein 90 (HSP90).

Hsp70/Hsp90 chaperone machinery is involved in the assembly of the purinosome

“…In addition, these chaperones have been demonstrated to participate in the formation and stabilization of protein complexes (16,17) and have recently emerged as important targets for cancer chemotherapeutics (18,19). To investigate whether the Hsp70/ Hsp90 machinery plays a role in the assembly of the purinosome, we first determined whether these proteins colocalize with In addition, both Hsp70 and Hsp90 were shown to be dynamically associated with the purinosomes as purine levels changed in the media ( Fig.…”

Structure of GPN-Loop GTPase Npa3 and Implications for RNA Polymerase II Assembly

“…In contrast, biogenesis of the 12-subunit Pol II complex remains poorly understood. It was shown previously that Pol II biogenesis requires the R2TP/ Prefoldin-like complex and the ATPase Hsp90 (4), a chaperone Table S1 in the supplemental material for a list of all peptides, Table S2 in the supplemental material for a list of all peptides that interact with Npa3, and that is involved in the assembly of several protein complexes (42), but additional factors are likely involved in Pol II assembly.…”

Nitric oxide and heat shock protein 90 activate soluble guanylate cyclase by driving rapid change in its subunit interactions and heme content

“…hsp90 is a ubiquitously expressed, ATP-dependent chaperone that helps to fold, stabilize, or modify the functions of select client proteins (12,13). We recently found that hsp90 drives heme insertion into sGC during its maturation in cells (14).…”