title: Assembly of the C1 complex.
abstract: The C1 complex of complement is a Ca(2+)-dependent complex protease comprising two loosely interacting subunits. C1q, the recognition subunit, is an hexameric protein with six peripheral globular domains, each connected through collagen-like "arms" to a central fibril-like "stalk". The catalytic subunit, C1s-C1r-C1r-C1s, is a Ca(2+)-dependent tetrameric association of two serine protease zymogens, C1r and C1s, that are sequentially activated by cleavage of a single peptide bond, upon binding of C1 to activators. Each monomeric protease is comprised of six structural motifs which form at least four domains, distributed in two functionally distinct regions, alpha (N-terminal) and gamma-B (C-terminal). The catalytic (gamma-B) regions of C1r and C1s are respectively located in the centre and at each end of the isolated tetramer, and the Ca(2+)-dependent C1r-C1s associations are mediated by the interaction (alpha) regions, which contain one Ca2+ binding site each. Physicochemical and electron microscopy studies indicate that the tetramer, which is highly elongated, folds into a more compact conformation upon interaction with C1q. Various models for C1 have been proposed, in which the tetramer either interacts with the outside part of the C1q arms (O- and W-shaped models), or is folded within the C1q arms (S- or 8-shaped models). These models are discussed in light of available information and in consideration of the structural requirements of C1 activation and function.
authors.affiliation: Laboratoire d'Enzymologie Moléculaire, Institut de Biologie Structurale, Grenoble, France.
authors.forename: G J
authors.initials: GJ
authors.lastname: Arlaud
authors.forename: N M
authors.initials: NM
authors.lastname: Thielens
authors.forename: C
authors.initials: C
authors.lastname: Illy
mesh_terms: D003172:Complement C1 / Q000096:biosynthesis* / Q000737:chemistry*; D015923:Complement C1r / Q000096:biosynthesis / Q000737:chemistry; D003173:Complement C1s / Q000096:biosynthesis / Q000737:chemistry; D006801:Humans; D046911:Macromolecular Substances; D008961:Models, Structural; D011487:Protein Conformation
chemical_list: D003172:Complement C1; D046911:Macromolecular Substances; D015923:Complement C1r; D003173:Complement C1s