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 was seen at pH 3.6-4.5; modest cleavage remained at pH 5.0, and no cleavage was detected above pH 5.0. Amino terminal sequencing of the major cleavage fragments 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' residues at the 2 CH2 cleavage sites were Phe254-Leu255 and Leu325-Thr326, indicating a preference by the schistosome protease for bulky hydrophobic residues flanking the scissile bond. No cleavage of the immunoglobulin light chain was detected. In addition, the recombinant schistosome protease indiscriminately 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 highlight the broad range digestive specificity of the enzyme which may play a role in the degradation of host serum proteins ingested as part of the schistosome bloodmeal.
Verity
C K
CK
Division of Infectious Diseases and Immunology and The CRC for Vaccine Technology, The Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Australia. christiV@qimr.edu.au
Loukas
A
A
McManus
D P
DP
Brindley
P J
PJ
D000595:Amino Acid Sequence; D000818:Animals; D002402:Cathepsin D / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D003176:Complement C3 / Q000378:metabolism*; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D012549:Schistosoma japonicum / Q000201:enzymology* / Q000235:genetics; D012709:Serum Albumin / Q000378:metabolism*
D003176:Complement C3; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D012709:Serum Albumin; D002402:Cathepsin D