The effects of iodine and thiol-blocking reagents on complement component C2 and on the assembly of the classical-pathway C3 convertase.
I2 can react with complement component C2 in a two-stage process. In the first stage, a form of C2 with enhanced haemolytic activity is produced. This form of C2 is cleaved to C2a and C2b by C1s at the same rate as native C2. The enhanced C2 haemolytic activity correlates with the ability to form a stable fluid-phase C3 convertase on addition of the C2 to C4b and C1s. It reflects an increased affinity for C4b of C2a formed from I2-treated C2, although the affinity for C4b of I2-treated C2 itself is not markedly increased. The specific activity of C3 convertase formed from I2-treated C2 is the same as that formed from native C2. The second stage of the reaction with I2, which is favoured at high pH or in the presence of excess I2, inactivates C2 on production of a species that cannot be cleaved by C1s. The presence of a single free thiol group in C2, which is the site of modification by I2, was confirmed by titration with p-chloromercuribenzoate, iodoacetamide and 5,5'-dithiobis-(2-nitrobenzoic acid). A single thiol group is also present in Factor B, and the cysteine residue, like that in C2, requires denaturation of the protein before reaction with iodoacetamide and 5,5'-dithiobis-(2-nitrobenzoic acid) but not p-chloro- mercuribenzoate .
D002729:Chloromercuribenzoates / Q000494:pharmacology; D003166:Complement Activating Enzymes / Q000378:metabolism*; D003167:Complement Activation / Q000187:drug effects*; D003173:Complement C1s; D003175:Complement C2 / Q000378:metabolism*; D050577:Complement C3-C5 Convertases / Q000378:metabolism*; D003181:Complement C4 / Q000378:metabolism; D015935:Complement C4b; D003171:Complement Pathway, Classical / Q000187:drug effects*; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007455:Iodine / Q000494:pharmacology*; D007460:Iodoacetamide / Q000494:pharmacology; D013439:Sulfhydryl Reagents / Q000494:pharmacology*; D020245:p-Chloromercuribenzoic Acid
D002729:Chloromercuribenzoates; D003175:Complement C2; D003181:Complement C4; D013439:Sulfhydryl Reagents; D020245:p-Chloromercuribenzoic Acid; D015935:Complement C4b; D007455:Iodine; D004228:Dithionitrobenzoic Acid; D003166:Complement Activating Enzymes; D050577:Complement C3-C5 Convertases; D003173:Complement C1s; D007460:Iodoacetamide