ROLE OF ACCESSORY PROTEINS IN PROTEIN-FOLDING

Within the past year, new insights have been gained into the structure and mechanism of protein disulfide isomerase and peptidyl prolyl cis-trans isomerase as true enzymes catalyzing rate-determining steps on the pathway of in vitro protein folding, The former enzyme, with its close structural similarity to thioredoxin, may serve both as an enzyme with broad substrate specificity and as a donor of redox equivalents. The latter enzyme has been isolated from many organisms and cell types and has been studied mainly as an 'immunophilin'. The three-dimensional structures of the enzyme-inhibitor complexes support the catalysis-by-distortion mechanism. Both enzymes are multifunctional; apart from being ubiquitous and abundant in the cell, clear evidence for their function as folding catalyst in vivo is still lacking. Structure formation of most proteins seems to involve molecular chaperones with different functions in the kinetic partitioning of folding, translocation and assembly. ATP participates in chaperone action as either a phosphorylating agent or an energy source. Chaperone-target interactions show low specificity. Various chaperone components seem to act synergistically, establishing 'chaperone pathways'.