The protein disulphide-isomerase family: unravelling a string of folds

The mammalian protein disulphide-isomerase (PDI) family encompasses several highly divergent proteins that are involved in the processing and maturati on of secretory proteins in the endoplasmic reticulum. These proteins are c haracterized by the presence of one or more domains of roughly 95-110 amino acids related to the cytoplasmic protein thioredoxin. All but the PDI-D su bfamily are composed entirely of repeats of such domains, with at least one domain containing and one domain lacking a redox-active -Cys-Xaa-Xaa-Cys- tetrapeptide. In addition to their known roles as redox catalysts and isome rases, the last few years have revealed additional functions of the PDI pro teins, including peptide binding, cell adhesion and perhaps chaperone activ ities. Attention is now turning to the non-redox-active domains of the PDIs , which may play an important role in all of the known activities of these proteins. Thus the presence of both redox-active and -inactive domains with in these proteins portends a complexity of functions differentially accommo dated by the various family members.