Bovine C4b binding protein. Molecular cloning of the alpha- and beta-chains provides structural background for lack of complex formation with protein S.
C4b binding protein (C4BP) regulates the complement system. It also interacts with anticoagulant protein S and with serum amyloid P component. Human C4BP is composed of seven identical 70-kDa alpha-chains and one 45-kDa beta-chain. The binding site for C4b is located on the alpha-chain, whereas the beta-chain binds protein S. Nothing is known about the structure and function of bovine C4BP. No complexed form of protein S was detected by using a gel filtration chromatography system combined with Western blotting. Bovine cDNA clones encoding the C4BP alpha- and beta-chains were isolated from a bovine liver cDNA library. Three overlapping alpha-chain clones predicted a 562-amino acid residues-long mature polypeptide. The overall amino acid sequence similarity with the human alpha-chain was 61%. Like its human counterpart, the bovine alpha-chain is composed of eight contiguous short consensus repeat units, each of approximately 60 amino acid residues, and a carboxyl-terminal nonrepeat region. One bovine beta-chain clone was found and characterized. It predicted a mature bovine beta-chain of 181 amino acid residues. The identity with the human beta-chain was 65% at the amino acid level. A noteworthy difference between bovine and human beta-chains was that the bovine beta-chain only contained two short consensus repeats compared with three in human beta-chain. Sequence alignment indicates that the region corresponding to residues 1-60 (repeat 1) in the human beta-chain is absent in the homologous bovine polypeptide. Because the short consensus repeats of the human beta-chain contain the binding site for protein S, the lack of one repeat unit in the bovine beta-chain may provide a clue to the lack of complex formation between C4BP and protein S in bovine plasma.
Hillarp
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A
Department of Clinical Chemistry, University of Lund, Malmö General Hospital, Sweden.
Thern
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Dahlbäck
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B
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D002850:Chromatography, Gel; D003001:Cloning, Molecular; D006801:Humans; D016167:Integrin alphaXbeta2; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D017293:Protein S / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D002352:Carrier Proteins; D016167:Integrin alphaXbeta2; D017293:Protein S