Complement receptor type 3 (CR3) binds to an Arg-Gly-Asp-containing region of the major surface glycoprotein, gp63, of Leishmania promastigotes.
The major surface glycoprotein of Leishmania promastigotes, gp63, was isolated and reconstituted into a lipid membrane immobilized on the surface of 5-micron-diameter silica beads. These beads bound to the macrophage (MO), and the extent of binding correlated with the density of gp63 on the bead. The bead thus facilitated analysis of the binding specificity of a single ligand, gp63, without contribution from other molecules present on the surface of intact promastigotes. Plating of MO onto substrates coated with antibodies directed against several cell surface receptors indicated that the complement receptor CR3 was necessary for binding gp63. CR3 recognizes a portion of C3 that contains the sequence R G D. Since gp63 also contains such a sequence, we tested the ability of a synthetic peptide based on the R G D-containing region of gp63 to inhibit the binding of gp63 beads. The R G D-containing peptide from gp63 inhibited the binding of both gp63 beads and EC3bi to MO. Similarly, peptides previously shown to inhibit the binding of C3bi also inhibited the attachment of gp63 beads. The synthetic peptide from the R G D region of gp63 also reduced the binding of intact promastigotes to MO. These results indicate that gp63 binds directly to CR3.
Russell
D G
DG
Department of Pathology, New York University Medical Center, New York 10016.
Wright
S D
SD
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000502:physiology; D000953:Antigens, Protozoan / Q000276:immunology / Q000378:metabolism*; D001667:Binding, Competitive; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007893:Leishmania donovani / Q000276:immunology*; D007894:Leishmania mexicana / Q000276:immunology*; D007895:Leishmania tropica / Q000276:immunology*; D016177:Macrophage-1 Antigen; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008666:Metalloendopeptidases; D008969:Molecular Sequence Data; D011951:Receptors, Complement / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D000953:Antigens, Protozoan; D016177:Macrophage-1 Antigen; D011951:Receptors, Complement; D005340:Fibrinogen; D008666:Metalloendopeptidases; C055146:glycoprotein gp63, Leishmania