title: The killer molecule of complement.
abstract: Cell injury by complement occurs as a consequence of activation of either the classical or the alternative pathway on the surface of a cell. It is accomplished by the membrane attack complex (MAC). Its precursor proteins, C5, C6, C7, C8, and C9, are hydrophilic glycoproteins with Mr ranging from 70,000-180,000. When C5 is cleaved by the serine protease C5 convertase which covalently attaches to target cells, nascent C5b is produced and forms together with C6 a soluble and stable bimolecular complex (C5b,6). Upon binding of C5b,6 to C7 a trimolecular complex (C5b-7) is formed which expresses a metastable membrane-binding site. Membrane-bound C5b-7 constitutes the receptor for C8 and the tetramolecular C5b-8 complex binds and polymerizes C9. During the assembly process the proteins undergo hydrophilic-amphiphilic transition and the end product consists of C5b-8 (Mr approximately 550,000) and of tubular poly C9 (Mr approximately 1,100,000). The functional channel size varies but its maximal diameter is approximately 100 A. C9 polymerization appears to involve initial reversible association of several C9 molecules which is followed by temperature-dependent, constrained unfolding. Unfolded C9 monomers then associate laterally with each other and polymerization terminates with closure of the circular structure which consists of 12-18 C9 monomers. Amino acid composition and sequence indicate that the N-terminal half of the single chain C9 molecule is hydrophilic and the C-terminal half rather hydrophobic. Phospholipid-binding and insertion into membranes are functions of the C-terminal portion of the molecule. Control of the MAC is exerted by the S-protein (Mr 80,000) which binds to the forming complex and prevents its attachment to the cell membrane. Control is also exerted by certain species-specific membrane proteins which interfere with C5 convertase and C9 function.
mesh_terms: D001665:Binding Sites; D003166:Complement Activating Enzymes / Q000276:immunology; D003167:Complement Activation; D003182:Complement C5 / Q000276:immunology; D050776:Complement C5b; D003186:Complement C9 / Q000276:immunology; D015938:Complement Membrane Attack Complex; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D003165:Complement System Proteins / Q000276:immunology*; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology
chemical_list: D003182:Complement C5; D003186:Complement C9; D015938:Complement Membrane Attack Complex; D008565:Membrane Proteins; C040352:complement C9 polymer; D050776:Complement C5b; D003165:Complement System Proteins; D003166:Complement Activating Enzymes