ARGININE RESIDUES OF THE GLOBULAR REGIONS OF HUMAN C1Q INVOLVED IN THE INTERACTION WITH IMMUNOGLOBULIN-G

The immunoglobulin G binding site in the globular regions of human com plement subcomponent C1q has been investigated by chemical modificatio n of histidine residues with diethylpyrocarbonate and arginine residue s with phenylglyoxal and cyclohexane-1,2-dione (CHD). Only the modific ation of arginine residues with CHD fulfills the requirements of a spe cific modification without unwanted side reactions. Specific modificat ion of arginine residues with CHD results in loss of immune complex re cognition without affecting the binding of C1r2s2 to form C1. The gros s structure of C1q is not changed by CHD treatment, and immune complex binding is restored to 82% of the control upon NH2OH treatment. Enzym ic digestion and isolation of the modified peptides indicate that the modification by CHD of 4 to 5 arginine residues (A162, B114, B129, C15 6, and possibly B163) per C1q globular ''head'' abolishes the ability of C1q to interact with immune complexes. These residues define two ar eas (and possible binding sites for IgG) on the globular region of C1q : B114-B129 (site 1) and A162-(B163)-C156 (site 2). Sequence compariso n and solvent exposure predictive studies favor site 2 as the immunogl obulin G binding site on the globular regions of Clq, although the par ticipation of site 1 cannot be ruled out.