Heat‐shock proteins as molecular chaperones

Abstract

Functional proteins within cells are normally present in their native, completely folded form. However, vital processes of protein biogenesis such as protein synthesis and translocation of proteins into intracellular compartments require the protein to exist temporarily in an unfolded or partially folded conformation. As a consequence, regions buried when a polypeptide is in its native conformation become exposed and interact with other proteins causing protein aggregation which is deleterious to the cell. To prevent aggregation as proteins become unfolded, heat‐shock proteins protect these interactive surfaces by binding to them and facilitating the folding of unfolded or nascent polypeptides. In other instances the binding of heat‐shock proteins to interactive surfaces of completely folded proteins is a crucial part of their regulation. As heat shock and other stress conditions cause cellular proteins to become partially unfolded, the ability of heat‐shock proteins to protect cells against the adverse effects of stress becomes a logical extension of their normal function as molecular chaperones.

Influence of Escherichia coli chaperone DnaK on protein immunogenicity

“…It is well established that protein aggregation has the potential to contribute to immunogenicity 21. Furthermore, the principal function of HSPs is to mediate the correct folding of proteins inside the cell and therefore, by nature, they bind to partially unfolded proteins 20. We also noted that the ability of HSPs to enhance the immunogenicity of a co‐administered antigen is well‐documented, with the successful use of HSPs in vaccine development 15.…”

“…The impact of these HCPs on immunogenicity was not explored; however, within the 20 most abundant E. coli cell proteins in the preparation, three HSPs were identified: the 60 000 MW chaperonin GroEL, the chaperone ClpB and the 70 000 MW HSP DnaK. One of the key functions of HSPs is to bind hydrophobic regions on unfolded proteins to prevent aggregation and facilitate protein folding 20. As aggregates consist of partially unfolded proteins with exposed hydrophobic regions, it would be anticipated that HSPs are likely to bind with high affinity to these regions.…”

Quantitative proteomics and network analysis of SSA1 and SSB1 deletion mutants reveals robustness of chaperone HSP70 network in Saccharomyces cerevisiae

“…The HSP70 chaperone family, including SSA1/SSA2 and SSB1/SSB2 proteins, has been extensively studied in terms of evolutionary similarity 14, 15, 16 and functional similarity/redundancy via knock‐out models 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27. For example, Craig et al.…”

p53-dependent induction of WAF1 by cold shock in human glioblastoma cells

“…Cold shock-induced proteins (Csps) have been well studied in Escherichia coli (Goldstein et al, 1990;Jones and Inouye, 1994;Jones et al, 1996). In contrast to hsps which are protein chaperones to help to refold the non-native proteins, prevent their aggregation or direct protein degradation (review in Becker and Craig, 1994), Csps have been shown to be RNA chaperones to prevent the formation of secondary structures in RNA at low temperature (Jones et al, 1996;Jiang et al, 1997). To our knowledge, cold shock proteins have not yet been found in human cells, thus, the e ects of cold shock on mammalian cells are poorly documented.…”