title: C5 convertase of the alternative complement pathway: covalent linkage between two C3b molecules within the trimolecular complex enzyme.
abstract: C5 convertase of the alternative C pathway is a complex enzyme consisting of three C fragments--one molecule of a major fragment of factor B (Bb) and two molecules of a major fragment of C3 (C3b). Within this C3bBbC3b complex, the first C3b binds covalently to the target surface, and Bb, which bears a catalytic site, binds noncovalently to the first C3b. In the present investigation, we studied the nature of the convertase that is assembled on E surfaces and obtained evidence that the second C3b binds directly to the alpha'-chain of the first through an ester bond rather than to the target surface. Thus, the alternative pathway C5 convertase could be described as a trimolecular complex in which Bb binds noncovalently to a covalently linked C3b dimer. We also obtained evidence that not only the second C3b but also the first C3b participates in binding C5, that is, covalently-linked C3b dimer acts as a substrate-binding site. Because of this two-site binding, the convertase has a much higher affinity for C5 than the surrounding monomeric C3b molecules. Based on this evidence, a new model of the alternative pathway C5 convertase is proposed. Covalent association of two subunits and the bivalent binding of the substrate are then common properties of the alternative and classical pathway C5 convertases.
authors.affiliation: Department of Bacteriology, Osaka University Medical School, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Y
authors.initials: Y
authors.lastname: Takata
authors.forename: H
authors.initials: H
authors.lastname: Kozono
authors.forename: J
authors.initials: J
authors.lastname: Takeda
authors.forename: K S
authors.initials: KS
authors.lastname: Hong
authors.forename: K
authors.initials: K
authors.lastname: Inoue
mesh_terms: D000818:Animals; D003166:Complement Activating Enzymes / Q000302:isolation & purification / Q000378:metabolism; D003167:Complement Activation; D050577:Complement C3-C5 Convertases / Q000302:isolation & purification / Q000378:metabolism; D003179:Complement C3b / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D003182:Complement C5 / Q000378:metabolism; D003170:Complement Pathway, Alternative; D004910:Erythrocyte Membrane / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D008958:Models, Molecular; D011817:Rabbits; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000378:metabolism; D012756:Sheep
chemical_list: D003182:Complement C5; D046911:Macromolecular Substances; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D003179:Complement C3b; D003166:Complement Activating Enzymes; D050577:Complement C3-C5 Convertases