A synthetic peptide from complement protein C9 binds to CD59 and enhances lysis of human erythrocytes by C5b-9.
The membrane glycoprotein CD59 protects host cells from homologous complement attack by inhibiting the assembly of the membrane attack complex. CD59 binds to C8 and C9 in the nascent membrane attack complex and interferes with C9 membrane insertion and polymerization. We show here that a synthetic peptide from the putative C9 hinge region, postulated to be involved in the rearrangement of C9 globular domains during membrane insertion, binds specifically to CD59 and enhances lysis of human erythrocytes by the terminal complement C5b-9 complex. The peptide, C9H, caused a dose-dependent increase in the sensitivity of human erythrocytes to C5b-9-mediated lysis by interfering with the final C9 binding and/or membrane insertion step. C9H exhibited species-specificity, since it had no activity against guinea pig C8 and C9 or on the putative functional homologues of CD59 in guinea pig erythrocytes. A direct association between CD59 and C9H was suggested by two different binding experiments: C9H inhibited the binding of 125I-labeled CD59 to immobilized C9, and C9H immobilized to microtiter plates bound purified CD59 and selectively recognized CD59 from extracts of detergent-solubilized human erythrocyte membranes. These data indicate that the peptide C9H corresponds to a region of the CD59 binding site of C9.
Tomlinson
S
S
Department of Pathology, New York University Medical Center, NY 10016.
Whitlow
M B
MB
Nussenzweig
V
V
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism*; D001665:Binding Sites; D018957:CD59 Antigens; D003186:Complement C9 / Q000378:metabolism*; D003169:Complement Inactivator Proteins / Q000378:metabolism*; D015938:Complement Membrane Attack Complex / Q000502:physiology*; D006461:Hemolysis; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*
D015703:Antigens, CD; D018957:CD59 Antigens; D003186:Complement C9; D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex; D008562:Membrane Glycoproteins; D010446:Peptide Fragments