Hsp90 and Hsp70 chaperones: Collaborators in protein remodeling

Abstract

Heat shock proteins 90 (Hsp90) and 70 (Hsp70) are two families of highly conserved ATP-dependent molecular chaperones that fold and remodel proteins. Both are important components of the cellular machinery involved in protein homeostasis and participate in nearly every cellular process. Although Hsp90 and Hsp70 each carry out some chaperone activities independently, they collaborate in other cellular remodeling reactions. In eukaryotes, both Hsp90 and Hsp70 function with numerous Hsp90 and Hsp70 co-chaperones. In contrast, bacterial Hsp90 and Hsp70 are less complex; Hsp90 acts independently of cochaperones, and Hsp70 uses two co-chaperones. In this review, we focus on recent progress toward understanding the basic mechanisms of Hsp90-mediated protein remodeling and the collaboration between Hsp90 and Hsp70, with an emphasis on bacterial chaperones. We describe the structure and conformational dynamics of these chaperones and their interactions with each other and with client proteins. The physiological roles of Hsp90 in Escherichia coli and other bacteria are also discussed. We anticipate that the information gained from exploring the mechanism of the bacterial chaperone system will provide the groundwork for understanding the more complex eukaryotic Hsp90 system and its modulation by Hsp90 co-chaperones.

Molecular determinants of chaperone interactions on MHC-I for folding and antigen repertoire selection

“…The chaperone function may provide an important protein homeostasis mechanism, by stabilizing misfolded, aggregation-prone MHC-I species which form inside the cell (5,59) and are known to contribute to the onset of disease (60). This cellular function is often attributed to a class of generic chaperones known as holdases, which includes essential heat-shock proteins (61). Our deep mutagenesis data suggest that the TAPBPR holdase activity requires a minimally folded epitope on the MHC α 2 domain with a conserved disulfide ( Fig.…”

Omnipresent Maxwell's demons orchestrate information management in living cells

“…It binds RpoH, and gene htpG is in the rpoH regulon. The regular functional collaboration between HtpG and DnaK requires that the two chaperones directly interact (Genest et al ., ). Within the frame of the present work, we can predict that inhibiting ATPase activity would prevent recycling of the protein to its ground state and abolish its activity.…”

Promotion of hyperthermic-induced rDNA hypercondensation inSaccharomyces cerevisiae

“…Hsp90 family members exhibit receptor/kinase signal transduction activities and are well-established ATP-dependent foldases that promote protein maturation and thermic tolerance by ensuring proper folding of client proteins (Khurana et al, 2018; Morán Luengo et al, 2019; Genest et al, 2019). In addition, however, Hsp90 family members also exhibit ‘holdase’ functions independent of ATP binding/hydrolysis that include structural or scaffolding roles (Genest et al, 2019; Hoter et al, 2018; Csermely et al, 1998). In this light, we were particularly intrigued by early EM studies through which Hsp90 was localized to the nucleolus and onto chromatin fibrils (Biggiogera et al, 1996; Ohtani et al, 1995).…”

“…Here, we consider several possibilities regarding the mechanism through which HSP/C impact thermic-induced rDNA hypercondensation. Given the well-established role for HSP/C in stabilizing or refolding client proteins (Khurana et al, 2018; Morán Luengo et al, 2019; Genest et al, 2019), one plausible mode of action is through stabilization of an as yet undefined thermic-sensitive client protein required for rDNA hypercondensation. This client is unlikely to include cohesin or condensin, given that thermic stresses in HSP/C mutant cells result in increased rDNA axial loop lengths but not loss of either loop morphology (loops transitioning to puffs) or sister chromatid cohesion (one loop transitioning to two loops) (Shen and Skibbens, 2017a; Matos-Perdomo and Machín, 2018a).…”