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The N‐terminal segment of glyceraldehyde‐3‐phosphate dehydrogenase of Haemonchus contortus interacts with complements C1q and C3
Author(s) -
Vedamurthy G. V.,
Sahoo S.,
Devi I. K.,
Murugavel S.,
Joshi P.
Publication year - 2015
Publication title -
parasite immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 75
eISSN - 1365-3024
pISSN - 0141-9838
DOI - 10.1111/pim.12273
Subject(s) - haemonchus contortus , glyceraldehyde 3 phosphate dehydrogenase , biology , epitope , parasite hosting , western blot , biochemistry , microbiology and biotechnology , complement system , dehydrogenase , recombinant dna , enzyme , antigen , immunology , antibody , helminths , world wide web , computer science , gene
Summary Haemonchus contortus , an economically important blood‐sucking parasite of sheep and goats, survives the harsh host gut environment by secreting a number of proteins referred as excretory/secretory ( ES ) products. Glyceraldehyde‐3‐phosphate dehydrogenase ( GAPDH ), a glycolytic enzyme, is one of the components of H . contortus ES products. The parasite enzyme binds to complement C3 and inhibits its activity. In this study, the C3‐binding activity of the parasite GAPDH was mapped to the N‐terminal part of the enzyme by generating defined recombinant fragments of the protein. The N‐terminal fragment also trapped complement C1q but not C5 and inhibited complement‐mediated lysis of sensitized sheep erythrocytes. Competitive binding assay indicates different binding regions for C1q and C3 proteins. GAPDH stimulated proliferation of goat peripheral blood mononuclear cells in vitro and reacted with the sera from H. contortus ‐infected animals. However, the fragments of GAPDH did not stimulate cell proliferation nor reacted with the infected animal sera. Furthermore, denatured GAPDH failed to react with the infected animal sera in dot blot suggesting conformation‐dependent epitope. These results demonstrate an elegant strategy of the parasite to completely shut down complement activation and identify GAPDH as a promising target for future therapeutic intervention.