Characterization of a Trypanosoma cruzi C3 binding protein with functional and genetic similarities to the human complement regulatory protein, decay-accelerating factor.
Evasion of the complement system by microorganisms is an essential event in the establishment of infection. In the case of Trypanosoma cruzi, the causative agent of Chagas disease, resistance to complement-mediated lysis is a developmentally regulated characteristic. Infectious trypomastigotes are resistant to complement-mediated lysis in the absence of immune antibodies, whereas the insect forms (epimastigotes) are sensitive to lysis via the alternative complement pathway. We have purified a developmentally regulated, trypomastigote glycoprotein, gp160, and shown that it has complement regulatory activity. The T. cruzi gp160 restricts complement activation by binding the complement component C3b and inhibiting C3 convertase formation. The protein is anchored in the parasite membrane via a glycosyl phosphatidylinositol linkage, similar to the human complement regulatory protein, decay-accelerating factor. Using anti-gp160 antibodies we have isolated a bacteriophage lgt11 clone expressing a portion of the gp160 gene that shares significant DNA sequence homology with the human DAF gene. These results provide functional, biochemical, and genetic evidence that the T. cruzi gp160 is a member of the C3/C4 binding family of complement regulatory proteins, and that gp160 may provide the infectious trypomastigotes with a means of evading the destructive effects of complement.
Norris
K A
KA
Department of Molecular Genetics and Biochemistry, University of Pittsburgh, PA 15261.
Bradt
B
B
Cooper
N R
NR
So
M
M
D000818:Animals; D018958:CD55 Antigens; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D050577:Complement C3-C5 Convertases / Q000037:antagonists & inhibitors; D003179:Complement C3b / Q000378:metabolism*; D015935:Complement C4b / Q000378:metabolism; D006017:Glycolipids / Q000502:physiology; D017261:Glycosylphosphatidylinositols; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D010716:Phosphatidylinositols / Q000502:physiology; D015800:Protozoan Proteins / Q000032:analysis*; D012689:Sequence Homology, Nucleic Acid; D014349:Trypanosoma cruzi / Q000737:chemistry*
D018958:CD55 Antigens; D002352:Carrier Proteins; D006017:Glycolipids; D017261:Glycosylphosphatidylinositols; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010716:Phosphatidylinositols; D015800:Protozoan Proteins; D003179:Complement C3b; D015935:Complement C4b; D050577:Complement C3-C5 Convertases