Molecular cloning of rat C4b binding protein alpha- and beta-chains: structural and functional relationships among human, bovine, rabbit, mouse, and rat proteins.
The C4b binding protein (C4BP) functions as a regulator of the complement system by interacting with the activated form of the fourth complement component, C4b. Human C4BP also interacts with the anticoagulant protein S and the serum amyloid P component (SAP). It is composed of seven identical 70-kDa alpha-chains and one 45-kDa beta-chain. The alpha-chain contains a binding site for C4b, whereas the beta-chain contains the protein S binding site. Recent studies have shown rabbit and bovine plasma to lack a C4BP-protein S complex, and the mouse beta-chain gene to have evolved into a pseudogene. Using a gel filtration chromatography system in combination with Western blotting, we detected a complex between C4BP and protein S in rat plasma, similar to the complex known in human plasma. Using purified rat C4BP and SAP we were unable to detect any complex between the two proteins, but rat C4BP was able to form a complex with human SAP. Rat cDNA clones encoding the C4BP alpha- and beta-chains were isolated from a rat liver cDNA library. The rat alpha-chain cDNA predicted a mature polypeptide chain of 545 amino acid residues, whereas the beta-chain cDNA predicted a mature polypeptide of 243 amino acid residues. The overall amino acid sequence identities between the rat alpha-chain and the mouse, human, rabbit, and bovine alpha-chains were 64, 60, 59, and 52%, respectively. The identities between the rat beta-chain and the human and bovine beta-chains were 68 and 57%, respectively. The rat represents the first non-primate species in which the C4BP-protein S interaction has been found to be conserved.
Hillarp
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Department of Clinical Chemistry, Lund University, Sweden.
Wiklund
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H
Thern
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Dahlbäck
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B
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D003001:Cloning, Molecular; D003169:Complement Inactivator Proteins; D018076:DNA, Complementary / Q000235:genetics; D006023:Glycoproteins; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D017293:Protein S / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011951:Receptors, Complement / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015183:Restriction Mapping; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000683:Serum Amyloid P-Component / Q000378:metabolism
D003169:Complement Inactivator Proteins; D018076:DNA, Complementary; D006023:Glycoproteins; D046911:Macromolecular Substances; D017293:Protein S; D011951:Receptors, Complement; D000683:Serum Amyloid P-Component