Hillarp A, Wiklund H, Thern A, Dahlbäck B
Department of Clinical Chemistry, Lund University, Sweden.
J Immunol. 1997 Feb 1;158(3):1315-23.
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.
C4b结合蛋白（C4BP）通过与第四补体成分C4b的活化形式相互作用，发挥补体系统调节剂的功能。人C4BP还与抗凝血蛋白S和血清淀粉样蛋白P成分（SAP）相互作用。它由七条相同的70 kDaα链和一条45 kDaβ链组成。α链含有C4b结合位点，而β链含有蛋白S结合位点。最近的研究表明，兔和牛血浆中缺乏C4BP-蛋白S复合物，且小鼠β链基因已演变成假基因。我们使用凝胶过滤色谱系统结合蛋白质印迹法，在大鼠血浆中检测到C4BP与蛋白S之间的复合物，类似于人血浆中已知的复合物。使用纯化的大鼠C4BP和SAP，我们未能检测到这两种蛋白之间的任何复合物，但大鼠C4BP能够与人SAP形成复合物。从大鼠肝脏cDNA文库中分离出编码C4BPα链和β链的大鼠cDNA克隆。大鼠α链cDNA预测的成熟多肽链有545个氨基酸残基，而β链cDNA预测的成熟多肽有243个氨基酸残基。大鼠α链与小鼠、人、兔和牛α链之间的总体氨基酸序列同一性分别为64%、60%、59%和52%。大鼠β链与人及牛β链之间的同一性分别为68%和%。大鼠是首个被发现C4BP-蛋白S相互作用保守的非灵长类物种。
