METHIONINE MODIFICATION IMPAIRS THE C5-CLEAVAGE FUNCTION OF COBRA VENOM FACTOR-DEPENDENT C3 C5 CONVERTASE/

The complement-mediated lysis of guinea pig erythrocytes by cobra veno m factor (CVF) decreased by 50-60% within 2 min of treatment with 5 mM sodium periodate at 0 degrees C. This loss of activity paralleled mod ification of 3-4 Met; other amino acids and sugar residues of the olig osaccharide chains were not affected. Treatment with N-chlorosuccinimi de or chloramine-T under conditions that specifically modified 3-4 rea dily-oxidizable Met also caused 50-60% loss of CVF activity. The secon dary structure of CVF was not altered by these modifications. Methioni ne-modified CVF (MetCVF) supported the cleavage of factor B by factor D with equal efficiency as that of untreated CVF to form C3/C5 convert ase (MetCVF,Bb) of the alternative pathway. MetCVF,Bb and CVF,Bb were indistinguishable with respect to C3 cleavage. However, the C5-cleavag e ability of MetCVF,Bb was significantly lower than that of CVF,Bb. Th ese results suggest the involvement of Met in CVF binding of C5.