Structural homology of complement protein C6 with other channel-forming proteins of complement (membrane attack complex/nucleotide sequence/amino acid sequence/cytolytic proteins)

The amino acid sequence of the amino- terminal half of the complement protein C6 has been found to show overall structural homology with the homologous regions of the channel-forming proteins C7, C8a, C8fi, and C9. In addition, two specific cysteine-rich segments common to the amino-terminal regions of C7, C8a, C8fi, and C9 also occur in their expected positions in C6, suggesting functional signifi- cance. Two cDNA clones encoding C6 were isolated from a human liver library in the bacteriophage vector Agtll. The predicted protein sequence contains an apparent initiation methionine and a putative signal peptide of 21 residues, as well as a site for N-glycosylation at residue 303. The sequence of the C6 protein reported here has 47-52% similarity with C7, C8a, C8fi, and C9, as well as 31-38% similarity with thrombospon- din, thrombomodulin, and low density lipoprotein receptor. The sequence data have been interpreted by using computer algorithms for estimation of average hydrophobicity and sec- ondary structure.