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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. cap alpha. subunit and C9

Journal Article · · Biochemistry; (United States)
DOI:https://doi.org/10.1021/bi00386a047· OSTI ID:6025082
A cDNA clone encoding the ..beta.. subunit (M/sub r/ 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 approx. 2.5 kb. This is similar to the message size for the ..cap alpha.. subunit of C8 and confirms the existence of different mRNAs for ..cap alpha.. and ..beta... This finding supports genetic evidence that ..cap 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. Determined of the carbohydrate composition indicated 1 or 2 asparagine-linked but no O-linked oligosaccharide chains. Comparison of the ..beta.. sequence to that reported earlier and to that of human C9 revealed a striking homology between all three proteins. For ..beta.. and ..cap 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/sup 5/, respectively. All three have a large internal domain that is nearly cysteine free and N- and C-termini that are cysteine-rich and homologous to the low-density lipoprotein receptor repeat and epidermal growth factor type sequences, respectively. The overall homology and similarities in size and structural organization are indicative of a close ancestral relationship. It is concluded that ..cap alpha.., ..beta.. and C9 are members of a family of structurally related proteins that are capable of interacting to produce a hydrophilic to amphiphilic transition and membrane association.
Research Organization:
Univ. of South Carolina, Columbia
OSTI ID:
6025082
Journal Information:
Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 26:12; ISSN BICHA
Country of Publication:
United States
Language:
English