Differential binding of IgG and of a HIV gp41 peptide by the B chain and A chain globular head sequences of C1q, respectively.

Two individual globular head regions (ghA and ghB) of the heterotrimeric C1q molecule (containing A, B, and C chains) were expressed in a bacterial expression system using a coproduction with the bacterial chaperone GroESL. The purified proteins were soluble and monomeric, as shown by gel-filtration analysis. No association into homotrimers was seen, which indicates that the ability to form heterotrimers is coupled with the discrimination against homotrimeric self-association. The individual globular heads retained their binding activities toward two ligands bound by the whole C1q molecule, i.e., IgG and the peptide P(601-613) derived from the HIV envelope glycoprotein gp41. The differential binding activities displayed for these ligands indicated a degree of structural independence of the binding sites from the regions responsible for heterotrimerization. It was found, using single chain recombinant anti-C1q Abs, that the binding sites on C1q for IgG and gp41 do not overlap, and this observation is also consistent with the view that specialization between the C1q polypeptide chains takes place within the C1q molecule regarding their ligand-binding activities.