Stress protein molecular chaperones

Stress protein molecular chaperones have already been introduced (see Chapter 6). Such proteins have a rich and varied molecular recognition and binding behaviour. Important examples include GroEL and the procollagen/collagen molecular chaperone protein known as heat shock protein 47 (Hsp47). 

Feder, M.E., and G.E. Hofmann (1999). Heat-shock proteins, molecular chaperones and the stress response Evolutionary and ecological physiology. Annu. Rev. Physiol. 61 243-282. 

Benjamin IJ and McMillan DR (1998) Stress (heat shock) proteins Molecular chaperones in cardiovascular biology and disease. Circulation Research 83 117-132. 

Molecular chaperones, stress proteins (note not all stress proteins are molecular chaperones and not all molecular chaperones are stress proteins) Heat shock proteins (Hsp) Polypeptide chain binding proteins... 

Hsp90 is a molecular chaperon required for the refolding of proteins in cells exposed to environmental stress. It contains an ATP-binding pocket in its amino terminus. Several natural products, for example radicicol (230) (Scheme 48), bind to this pocket and inhibit its chaperon function, which is mirrored in enhanced proteosomal degradation of Hsp90 client proteins, so that compounds like 230 are of interest as novel anticancer agents. 

The efficient uptake of precursor proteins depends on their presentation in a translocation competent state. This is maintained in vivo by the specific interaction with a highly conserved group of proteins, the heat-shock or stress related proteins (hps70s). These act as molecular chaperones and interact with the proteins to maintain them in a correctly folded state, a process which is ATP dependent. 

Synthesis of molecular chaperones may be constitutive or stress-induced. Several size classes of molecular chaperones are synthesized constitutively to facilitate the housekeeping functions associated with protein synthesis and maturation. All organisms contain constitutively expressed chaperones, and the ubiquitous occurrence of these proteins is strong reason to believe that they appeared very early in evolution. Orthologs of some classes of molecular chaperones are found in prokaryotes and all eukaryotes. 

Cold stress may induce synthesis of heat-shock (stress) proteins. Exposure of cells to cold shock may lead to the induction of one or more of the classes of molecular chaperones that also are induced by heat shock. This is strong evidence that low temperature, like high temperature, can lead to non-native protein structures in vivo and, therefore, to the requirement for enhanced chaperoning activity. Induction of cold-induced protein chaperones has been seen in bacteria (Salotra et al., 1995), in whole organism studies of ectothermic animals (Petersen et al., 1990 Yocum et ah, 1991),... 

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