THE ONCHOCERCA-VOLVULUS HOMOLOG OF THE MULTIFUNCTIONAL POLYPEPTIDE PROTEIN DISULFIDE-ISOMERASE

Protein disulfide isomerase (PDI) functions to catalyze the formation of correct disulfide bonds in nascent proteins, and also acts as one o f the subunits of prolyl-4 hydroxylase, the enzyme responsible for the oxidative maturation of procollagen. Since the cuticle of parasitic n ematodes consists primarily of a network of collagen molecules which a re connected through intermolecular disulfide bonds, PDI might be expe cted to be involved in the process of cuticle biosynthesis. The isolat ion and characterization of a cDNA encoding the PDI homologue of Oncho cerca volvulus is described. This cDNA contains a single, long open re ading frame that encodes sequence motifs identical to the two known ac tive sites of PDI for isomerase activity. The O. volvulus PDI appears to be encoded by a single copy gene. Both in situ hybridization and im munolocalization data suggest that PDI is both spatially and temporall y regulated in O. volvulus. The pattern of spatial and temporal regula tion is consistent withe the involvement of PDI in the biosynthesis of the parasite cuticle. The parasite protein appears to be an antigen r ecognized by a minority of individuals exposed to O. volvulus.