Conformational changes in complement component C4 induced by activation, treatment with amines, chaotropes, or freezing-thawing, detectable by radioiodination using lactoperoxidase.

Conversion of C4 to C4b by enzymic cleavage or generation of a C4b-like form by treatment with amines, chaotropes, or freezing and thawing is accompanied by conformational alterations in the molecule. The nature of the changes is the same whether C4 is converted to a C4b-like form or to C4b. Evidence for structural changes at the surface of the C4 molecule was obtained by peripheral labeling with 125I by the lactoperoxidase method: there are residues, probably tyrosines, that are inaccessible for radioiodination in C4b and C4b-like C4, but exposed in native C4. The residues concerned are located in two separated parts of the alpha-chain at a distance of approximately 9000-34,000 m.w. from the N-terminus and in a 16,000 m.w. portion at the C-terminus. It is so far unknown whether the observed changes are involved in the uncovering of new binding sites, or whether they are the mere reflection of alterations elsewhere in the molecule that are of greater functional significance.