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 complement subcomponent C1q has been investigated by chemical modification of histidine residues with diethylpyrocarbonate and arginine residues with phenylglyoxal and cyclohexane-1,2-dione (CHD). Only the modification of arginine residues with CHD fulfills the requirements of a specific modification without unwanted side reactions. Specific modification of arginine residues with CHD results in loss of immune complex recognition without affecting the binding of C1r2S2 to form C1. The gross structure of C1q is not changed by CHD treatment, and immune complex binding is restored to 82% of the control upon NH2OH treatment. Enzymic digestion and isolation of the modified peptides indicate that the modification by CHD of 4 to 5 arginine residues (A162, B114, B129, C156, and possibly B163) per C1q globular "head" abolishes the ability of C1q to interact with immune complexes. These residues define two areas (and possible binding sites for IgG) on the globular region of C1q: B114-B129 (site 1) and A162-(B163)-C156 (site 2). Sequence comparison and solvent exposure predictive studies favor site 2 as the immunoglobulin G binding site on the globular regions of C1q, although the participation of site 1 cannot be ruled out.
Marqués
G
G
Departamento de Inmunología, Fundación Jiménez Díaz, Madrid, Spain.
Antón
L C
LC
Barrio
E
E
Sánchez
A
A
Ruiz
S
S
Gavilanes
F
F
Vivanco
F
F
D000595:Amino Acid Sequence; D000818:Animals; D000936:Antigen-Antibody Complex; D001120:Arginine; D001666:Binding Sites, Antibody; D002851:Chromatography, High Pressure Liquid; D015922:Complement C1q / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D003512:Cyclohexanones / Q000494:pharmacology; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology; D006639:Histidine; D006801:Humans; D019811:Hydroxylamine; D006898:Hydroxylamines / Q000494:pharmacology; D007074:Immunoglobulin G / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000302:isolation & purification; D010658:Phenylglyoxal / Q000494:pharmacology; D011487:Protein Conformation; D011817:Rabbits
D000936:Antigen-Antibody Complex; D003512:Cyclohexanones; D006898:Hydroxylamines; D007074:Immunoglobulin G; D046911:Macromolecular Substances; D010446:Peptide Fragments; D019811:Hydroxylamine; D006639:Histidine; C018031:1,2-cyclohexanedione; D015922:Complement C1q; D001120:Arginine; D004047:Diethyl Pyrocarbonate; D010658:Phenylglyoxal