title: The binding site for C1q on IgG.
abstract: In humoral defence, pathogens are cleared by antibodies acting as adaptor molecules: they bind to antigen and trigger clearance mechanisms such as phagocytosis, antibody-dependent cell-mediated cytotoxicity and complement lysis. The first step in the complement cascade is the binding of C1q to the antibody. There are six heads on C1q, connected by collagen-like stems to a central stalk, and the isolated heads bind to the Fc portion of antibody rather weakly, with an affinity of 100 microM (ref. 3). Binding of antibody to multiple epitopes on an antigenic surface, aggregates the antibody and this facilitates the binding of several C1q heads, leading to an enhanced affinity of about 10 nM (ref. 1). Within the Fc portion of the antibody, C1q binds to the CH2 domain. The interaction is sensitive to ionic strength, and appears to be highly conserved throughout evolution as C1q reacts with IgG from different species (for example see ref. 8). By systematically altering surface residues in the mouse IgG2b isotype, we have localized the binding site for C1q to three side chains, Glu 318, Lys 320 and Lys 322. These residues are relatively conserved in other antibody isotypes, and a peptide mimic of this sequence is able to inhibit complement lysis. We propose that this sequence motif forms a common core in the interactions of IgG and C1q.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Duncan
authors.forename: G
authors.initials: G
authors.lastname: Winter
mesh_terms: D000818:Animals; D001665:Binding Sites; D003166:Complement Activating Enzymes / Q000235:genetics / Q000276:immunology*; D003172:Complement C1 / Q000235:genetics / Q000276:immunology*; D015922:Complement C1q; D006461:Hemolysis; D006801:Humans; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D003172:Complement C1; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D015922:Complement C1q; D003166:Complement Activating Enzymes