title: Domain structure and associated functions of subcomponents C1r and C1s of the first component of human complement.
abstract: The serine protease subcomponents of the activated form of the first component of human complement (C1), C1r and C1s, were observed by electron microscopy after the native proteins and their limited proteolysis products, obtained from autolytic cleavage (C1r) or from incubation with plasmin (C1s) were rotary shadowed. At the monomeric level, both C1r and C1s comprised two globular domains, a smaller interaction domain (corresponding to the NH2-terminal half of the A chain, alpha, and responsible for calcium binding and C1r-C1s interaction) and a larger catalytic domain (corresponding to the COOH-terminal part of the A chain, gamma, disulfide-linked to the B chain and bearing the serine protease active site). The two globular domains are linked by a connecting strand, beta. The (C1r)2 dimer appeared as a "croissant"-like association, where the two monomers interact through their catalytic domains. On the basis of the domain structure of C1r and C1s, a model of the calcium-dependent C1s dimer is proposed, in which the two monomers interact through their NH2-terminal interaction domains; in the same way, a model of the C1s-(C1r)2-C1s catalytic subunit of C1 is presented, in which (C1r)2 forms a core, its distal interaction domains interacting with the corresponding domains of C1s.
authors.forename: C L
authors.initials: CL
authors.lastname: Villiers
authors.forename: G J
authors.initials: GJ
authors.lastname: Arlaud
authors.forename: M G
authors.initials: MG
authors.lastname: Colomb
mesh_terms: D003166:Complement Activating Enzymes / Q000032:analysis*; D015923:Complement C1r; D003173:Complement C1s; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D007531:Isoflurophate / Q000494:pharmacology; D007700:Kinetics; D008854:Microscopy, Electron; D008958:Models, Molecular; D008970:Molecular Weight; D010447:Peptide Hydrolases / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D007531:Isoflurophate; D003166:Complement Activating Enzymes; D010447:Peptide Hydrolases; D015923:Complement C1r; D003173:Complement C1s; D005341:Fibrinolysin