Glyceraldehyde-3-phosphate dehydrogenase of the parasitic nematode Haemonchus contortus binds to complement C3 and inhibits its activity.
Haemonchus contortus is an economically important gastrointestinal parasite that infects primarily sheep and goats. To survive inside the host, the parasite must overcome the host immune response. In this study, we have identified and characterized a complement-C3-binding protein (H.c-C3BP) from this parasite employing biochemical and molecular biology tools. Initially, a truncated form of the protein was isolated from the excretory-secretory products of the parasite using C3-Sepharose column that facilitated its identification by mass spectroscopy. Subsequently, the parent molecule was generated in E. coli, and sequence analysis confirmed it as glyceraldehyde-3-phosphate dehydrogenase (GAPDH). GAPDH reacted with the antiserum raised against the truncated protein, and the truncated protein reacted with anti-GAPDH antiserum. The protein inhibited complement function as measured by haemolytic assay and membrane attack complex (MAC) formation. Sera from H. contortus-infected animals reacted with GAPDH as well as the truncated form of the protein, which further lend support to protein secretion. Thus, the C3-binding property of H. contortus GAPDH is a new function, and it represents a new entity of complement-binding protein. Identification and characterization of H.c-C3BP should facilitate development of new therapeutics considering a key role of this protein in immune modulation.
Division of Biochemistry, Indian Veterinary Research Institute, Izatnagar, UP, India.
S
S
Sahoo
S
S
Murugavel
I K
IK
Devi
G V
GV
Vedamurthy
S C
SC
Gupta
B P
BP
Singh
P
P
Joshi
D000595:Amino Acid Sequence; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D003167:Complement Activation; D003176:Complement C3 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D015511:Goat Diseases / Q000276:immunology* / Q000469:parasitology; D006041:Goats / Q000276:immunology; D006188:Haemonchiasis / Q000276:immunology / Q000469:parasitology / Q000662:veterinary*; D006189:Haemonchus / Q000201:enzymology* / Q000276:immunology*; D015801:Helminth Proteins / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D006790:Host-Parasite Interactions; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D012756:Sheep / Q000276:immunology
D000909:Antibodies, Helminth; D003176:Complement C3; D015801:Helminth Proteins; D011994:Recombinant Proteins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases
GAPDH; H.c-C3BP; H. contortus; MAC; complement activity; immunomodulation