Complementary DNA and derived amino acid sequence of the beta subunit of human complement protein C8: identification of a close structural and ancestral relationship to the alpha subunit and C9.
A cDNA clone encoding the beta subunit (Mr 64,000) of the eighth component of complement (C8) has been isolated from a human liver cDNA library. This clone has a cDNA insert of 1.95 kilobases (kb) and contains the entire beta sequence [1608 base pairs (bp)]. Analysis of total cellular RNA isolated from the hepatoma cell line HepG2 revealed the mRNA for beta to be approximately 2.5 kb. This is similar to the message size for the alpha subunit of C8 and confirms the existence of different mRNAs for alpha and beta. This finding supports genetic evidence that alpha and beta are encoded at different loci. Analysis of the derived amino acid sequence revealed several membrane surface seeking segments that may facilitate beta interaction with target membranes during complement-mediated cytolysis. Determination of the carbohydrate composition indicated 1 or 2 asparagine-linked but no O-linked oligosaccharide chains. Comparison of the beta sequence to that reported for alpha in the preceding paper [Rao, A. G., Howard, O. M. Z., Ng, S. C., Whitehead, A. S., Colten, H. R. & Sodetz, J. M. (1987) Biochemistry (preceding paper in this issue)] and to that of human C9 revealed a striking homology between all three proteins. For beta and alpha, the overall homology is 33% on the basis of identity and 53% when conserved substitutions are allowed. For beta and C9, the values are 26% and 47%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Howard
O M
OM
Department of Chemistry and School of Medicine, University of South Carolina, Columbia 29208.
Rao
A G
AG
Sodetz
J M
JM
D000595:Amino Acid Sequence; D001483:Base Sequence; D005075:Biological Evolution; D003185:Complement C8 / Q000235:genetics*; D003186:Complement C9 / Q000235:genetics*; D004247:DNA / Q000032:analysis*; D004262:DNA Restriction Enzymes; D006801:Humans; D008099:Liver / Q000378:metabolism; D046911:Macromolecular Substances; D008970:Molecular Weight; D012689:Sequence Homology, Nucleic Acid
D003185:Complement C8; D003186:Complement C9; D046911:Macromolecular Substances; D004247:DNA; D004262:DNA Restriction Enzymes