Transmembrane channel-formation by five complement proteins.
Five serum proteins act in concert to form the membrane attack complex (MAC) of complement. The precursor proteins, C5, C6, C7, C8 and C9, are hydrophilic glycoproteins with molecular weights ranging from 70,000 to 180,000. When C5 is cleaved by the serine protease C5 convertase, nascent C5b is produced which 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 approx. 550,000) and of tubular poly C9 (Mr approx. 1,100,000). The functional channel size varies but its maximal diameter is approximately 10 nm. C9 polymerization appears to involve initial reversible associations of several C9 molecules, which leads to 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.
D000595:Amino Acid Sequence; D001665:Binding Sites; D003166:Complement Activating Enzymes / Q000378:metabolism; D050577:Complement C3-C5 Convertases; D003185:Complement C8 / Q000378:metabolism; D003186:Complement C9 / Q000378:metabolism; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D008854:Microscopy, Electron; D008970:Molecular Weight; D010743:Phospholipids / Q000378:metabolism
D003185:Complement C8; D003186:Complement C9; D015938:Complement Membrane Attack Complex; D007473:Ion Channels; D010743:Phospholipids; D003165:Complement System Proteins; D003166:Complement Activating Enzymes; D050577:Complement C3-C5 Convertases