title: New insights into the molecular mechanisms of classical complement activation.
abstract: C1q, the initiator of the classical complement cascade, is a versatile molecule with numerous ligands and variety of functions. Recent mutagenesis, epitope mapping and structural data brought novel understanding of the molecular mechanisms of C1q binding to target molecules, and subsequent C1 activation. Evidence has emerged suggesting that residues located within the C1q apical surface, and the exposed side surface of the B chain, facilitate the interaction of C1q with the majority of C1q ligands. The binding of C1q to IgG, IgM, CRP, and PTX3 is most likely a contiguous process, developing in different phases. During the initial phase, residues located within the gC1q apex, and shared between the three chains, are involved in the interaction with the ligands. After this initial recognition event, the Ca(2+) ion is attracted by the negatively charged C1q ligand. This loss of the Ca(2+) ion induces a rotation of the globular C1q head, facilitating further ligand binding, and transmitting an activation signal to C1r-C1s. This review summarizes these data, and offers a unifying model for C1 activation by negatively charged gC1q targets.
authors.affiliation: Department of Biochemistry, Sofia University, Sofia 1461, Bulgaria.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Kojouharova
authors.forename: Kenneth
authors.initials: K
authors.lastname: Reid
authors.forename: Mihaela
authors.initials: M
authors.lastname: Gadjeva
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D015922:Complement C1q / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003171:Complement Pathway, Classical / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding
chemical_list: D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015922:Complement C1q