| Heat shock proteins (also known as stress proteins) constitute a family of highly conserved and abundant proteins present in all living organisms investigated thus far. While present in cells growing under normal conditions, exposure to certain forms of stress such as heat shock, nutrient deprivation, or virus infections, leads to their increased levels. Hsps of different molecular sizes range from 10 kDa to 100 kDa have been found in eukaryotic cells; the most characterized families of eukaryotic hsps being hsp90, hsp70, and hsp60. Hsps, in general, interact with misfolded/unfolded proteins and help in their folding, assembly, and translocation within the cell. Due to their function, these proteins are also termed "molecular chaperones" or polypeptide chain binding proteins.The hsp70 family, which is perhaps the best梒haracterized family of hsps, is highly conserved throughout evolution. The hsp70 homolog in E.coli, Dnak, has 45-50% amino acid similarity when compared with any of its eukaryotic counterparts; Themselves products of highly conserved multiple genes (sharing 50-95% sequence identity at the nucleotide level). In mammals, the most well characterized member of the hsp70 family include a constitutive member (heatshock cognate 70 or hsc 70), a stress-inducible member (hsp70, whose expression is largely dependent upon application of stress, such as heat shock), an endoplasmic reticulum localized member known as BiP (or grp78) , and an hsp70 member present in the mitochondria! matrix of cells. Various hsp70 proteins have been shown to play multiple roles within the cell including: promotion of folding/assembly of certain proteins into their native structures, translocation of polypeptides to organelles within the cell, targeting of aged proteins to lysosomes for degradation, and dissolution of insoluble protein aggregates. It can be expected that inducible hsp70 performs functions similar to constitutive hsp70 (hsc70) but with additional stress-related roles, particularly, as a chaperonin in folding and solubilization of denatured protein aggregates and in the translocation of irreversibly damaged proteins which often occurs in stress conditions.Despite extensive research on hsp70 proteins, the mechanism of their action is still poorly understood. Hsp70 proteins have been proposed to have a two-domain structure: the N terminal domain binds adenine nucleotides, and the C terminal domain binds short segments of extended polypeptides. Certain hsp70 members exhibit a weak ATPase activity when an appropriate substrate such as a protein or a synthetic peptide is provided. Polypeptide substrate binding to hsp70 requires the presence of ADP whereas the release of polypeptide is facilitated by binding of ATP. This nucleotide-dependent cycle of polypeptide chain binding and release leads to correct folding of proteins and may also account for the other diverse functions associated with hsp70.Hsps have also been identified as dominant antigens in many bacterial and parasitic infections. Antibodies that recognize hsp70 have been identified in the sera of patients with malaria, trypanosomiasis. leishmaniasis, schistosomiasis, and filariasis. In addition, T cell responses to hsp70 members have been observed in certain parasitic infections and autoimmune disease.Certain hsp members have been implicated as targets of immunosuppressivedrugs, e.g., a potent immunosupressant, deoxyspergualin has been demonstrated to specifically bind hsc70. Recently years, it has been suggested that hsp70 may play a role as a carrier molecule in eliciting immune responses to certain peptide antigens when bound to or crosslinked to hsp70. In addition, the induction of hsp70 in a cell under stress has been suggested to elicit cytoprotective effects against similar or other forms of stress. The cytoprotective role of hsp70 during tissue damage caused by ischemia and certain neuronsl injuries has been observed.To facilitate structural and functional studies on human hsp70 and to further investigate the immune response...
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