BINDING OF HUMAN-COMPLEMENT COMPONENT C4B-BINDING PROTEIN (C4BP) TO STREPTOCOCCUS-PYOGENES INVOLVES THE C4B-BINDING SITE

A key step in the elimination of invading pathogens from the body is t he covalent binding of complement proteins C3b and C4b to their surfac e, However, many pathogens have evolved mechanisms to avoid the comple ment system of the host, Understanding how these mechanisms work may l ead to more efficacious forms of therapy, Here we provide an insight i nto the molecular basis of how Streptococcus pyogenes binds human plas ma C4b-binding protein (hC4BP), a complement regulatory molecule that may decrease C3b and C4b deposition on the streptococcal surface. We s how that streptococcal surface molecules bind to a site on hC4BP that is indistinguishable from the C4b binding site. This site involves mul tiple binding surfaces that span short consensus repeats 1 to 3 of the alpha-chain of hC4EP. We propose that hC4BP is bound to the bacterial surface because the streptococcal surface molecules involved in the i nteraction mimic human C4b epitopes.