A family of secreted mucins from the parasitic nematode Toxocara canis bears diverse mucin domains but shares similar flanking six-cysteine repeat motifs

Infective larvae of the parasitic nematode Toxocara canis secrete a family of mucin-Like glycoproteins, which are implicated in parasite immune evasio n. Analysis of T. canis expressed sequence tags identified a family of four mRNAs encoding distinct apomucins (Tc-muc-1-4), one of which had been prev iously identified in the TES-120 family of glycoproteins secreted by this p arasite. The protein products of all four cDNAs contain signal peptides, a repetitive serine/threonine-rich tract, and varying numbers of 36-amino aci d six-cysteine (SXC) domains. SXC domains are found in many nematode protei ns and show similarity to cnidarian (sea anemone) toxins. Antibodies to the SXC domains of TcMUG-1 and Tc-MUC-3 recognize differently migrating member s of TES-120. TES-120 proteins separated by chromatographic methods showed distinct amino acid composition, mass, and sequence information by both Edm an degradation and matrix-assisted laser desorption ionization/time of flig ht mass spectrometry on peptide fragments. Tc-MUC-1, -2, and -3 were shown to be secreted mucins with real masses of 39.7, 47.8, and 45.0 kDa in contr ast to their predicted peptide masses of 15.7, 16.2, and 26.0 kDa, respecti vely. The presence of SXC domains in all mucin products supports the sugges tion that the SXC motif is required for mucin assembly or export. Homology modeling indicates that the six-cysteine domains of the T. canis mucins ado pt a similar fold to the sea anemone potassium channel-blocking toxin BgK, forming three disulfide bonds within each subunit.