Schistosoma japonicum cathepsin D aspartic protease cleaves human IgG and other serum components

Recombinant cathepsin D aspartic protease of Schistosoma japonicum cleaved human IgG in vitro in a time and dose-dependent manner. Optimal cleavage wa s seen at pH 3.6-4.5; modest cleavage remained at pH 5.0, and no cleavage w as detected above pH 5.0. Amino terminal sequencing of the major cleavage f ragments of human IgG identified a Fab fragment from the VH1 domain, and 2 cleavage sites in the CH2 domain below the hinge region. The P1 and P1' res idues at the 2 CH2 cleavage sites were Phe254-Leu255 and Leu325-Thr326, ind icating a preference by the schistosome protease for bulky hydrophobic resi dues flanking the scissile bond. No cleavage of the immunoglobulin light ch ain was detected. In addition, the recombinant schistosome protease indiscr iminately degraded the human serum proteins complement C3 and serum albumin into numerous small fragments. These results demonstrate specific cleavage of human IgG by the recombinant schistosome aspartic protease, and highlig ht the broad range digestive specificity of the enzyme which may play a rol e in the degradation of host serum proteins ingested as part of the schisto some bloodmeal.