Hsp70 chaperones: Cellular functions and molecular mechanism

Abstract

Abstract. Hsp70 proteins are central components of the cellular network of molecular chaperones and folding catalysts. They assist a large variety of protein folding processes in the cell by transient association of their substrate binding domain with short hydrophobic peptide segments within their substrate proteins. The substrate binding and release cycle is driven by the switching of Hsp70 between the low-affinity ATP bound state and the high-affinity ADP bound state. Thus, ATP binding andCMLS, Cell. Mol. Life Sci. 62 (2005) 670 -684 1420-682X/05/060670-15 DOI 10.1007/s00018-004-4464-6 © Birkhäuser Verlag, Basel, 2005 CMLS Cellular and Molecular Life Scienceshydrolysis are essential in vitro and in vivo for the chaperone activity of Hsp70 proteins. This ATPase cycle is controlled by co-chaperones of the family of J-domain proteins, which target Hsp70s to their substrates, and by nucleotide exchange factors, which determine the lifetime of the Hsp70-substrate complex. Additional co-chaperones fine-tune this chaperone cycle. For specific tasks the Hsp70 cycle is coupled to the action of other chaperones, such as Hsp90 and Hsp100.

Highly specific host-pathogen interactions influence Metarhizium brunneum blastospore virulence against Culex quinquefasciatus larvae

“…[55] These proteins function as general molecular chaperones that maintain or return proteins to their functional state, minimize aggregation of proteins in their non-native conformation, and target unfolded or aggregated proteins for degradation or removal [56]. HSP70  has vital housekeeping functions, maintaining homeostasis and protecting cells against thermal and oxidative stress [57] and was up-regulated in Culex larvae whether they had been infected with blastospores or conidia suggesting that HSP70 played a key role in stress management in mosquito larvae. Castillo et al [58] found that up-regulation of HSP genes is evidence of increasing stress in response to pathogen infection.…”

A 70-kDa molecular chaperone, DnaK, from the industrial bacterium Bacillus licheniformis: gene cloning, purification and molecular characterization of the recombinant protein

“…Hsp70s/DnaKs are composed of a highly homologous N-terminal ATPase domain, a substrate-binding domain and a C-terminal variable domain [5]. The molecular chaperone function of Hsp70/DnaK proteins seems to be based on its ATPase activity and this activity is stimulated by Hsp40/ DnaJ, GrpE and substrate binding [6].…”

Protein monoubiquitylation: targets and diverse functions

“…At least five proteins have been shown to be monoubiquitylated by Parkin. Two of these substrates are protein chaperones of the heat‐shock protein (Hsp) 70 family—Hsp70 and Hsc70—that facilitate the folding of newly synthesized proteins as well as the refolding of misfolded and aggregated proteins (Mayer & Bukau 2005; Moore et al . 2008).…”