A Schistosoma protein, Sh-TOR, is a novel inhibitor of complement which binds human C2.
Human complement regulatory (also called inhibitory) proteins control misdirected attack of complement against autologous cells. Trypanosome and schistosome parasites which survive in the host vascular system also possess regulators of human complement. We have shown Sh-TOR, a protein with three predicted transmembrane domains, located on the Schistosoma parasite surface, to be a novel complement regulatory receptor. The N-terminal extracellular domain, Sh-TOR-ed1, binds the complement protein C2 from human serum and specifically interacts with the C2a fragment. As a result Sh-TOR-ed1 pre-incubated with C2 inhibits classical pathway (CP)-mediated haemolysis of sheep erythrocytes in a dose-dependent manner. In CP-mediated complement activation, C2 normally binds to C4b to form the CP C3 convertase and Sh-TOR-ed1 has short regions of sequence identity with a segment of human C4b. We propose the more appropriate name for TOR of CRIT (complement C2 receptor inhibitory trispanning).
Inal
J M
JM
MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, UK. jameel.inal@unibas.ch
Sim
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RB
D000595:Amino Acid Sequence; D000818:Animals; D000947:Antigens, Helminth; D000953:Antigens, Protozoan / Q000737:chemistry / Q000378:metabolism*; D015153:Blotting, Western; D002846:Chromatography, Affinity; D003175:Complement C2 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D050678:Complement C2a; D050577:Complement C3-C5 Convertases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015935:Complement C4b / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D003171:Complement Pathway, Classical / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D015801:Helminth Proteins; D006461:Hemolysis / Q000276:immunology; D006801:Humans; D018448:Models, Immunological; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D012547:Schistosoma / Q000276:immunology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012756:Sheep
D000947:Antigens, Helminth; D000953:Antigens, Protozoan; D003175:Complement C2; D015801:Helminth Proteins; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C120046:TM3 protein, Schistosoma; D015935:Complement C4b; D050577:Complement C3-C5 Convertases; D050678:Complement C2a