Chakravarti D N, Campbell R D, Porter R R
Department of Biochemistry, University of Oxford, U.K.
Mol Immunol. 1987 Nov;24(11):1187-97. doi: 10.1016/0161-5890(87)90165-9.
The complete amino acid sequence of the C4d fragment (380 residues long) of the human complement component C4 is presented. Most of the sequence was determined by analysis of CNBr peptides and tryptic peptides obtained from S-carboxymethylated protein. The sequence of the amino terminal 88 residues [Campbell R. D., Gagnon J. and Porter R. R. (1981) Biochem. J. 199, 359-370] and a 106 residue polymorphic segment of C4d [Chakravarti D. N., Campbell R. D. and Gagon J. (1983) FEBS Lett. 154, 387-390] was extended. Some overlaps not provided by the protein sequence analysis were obtained from the amino acid sequence predicted by the nucleotide sequence [Belt K. T., Carroll M. C. and Porter R. R. (1984) Cell 36, 907-914]. The present protein sequence data provide information for the isolation of all the CNBr and succinylated tryptic peptides of C4d. In addition to the polymorphism previously described, two other sets of polymorphic amino acid residues at positions 153 (Ile/Ser) and 154 (Gln/Ala) have been identified. The major site of glycosylation has been shown to be an asparagine residue located in the sequence -Asn-Val-Thr- in the carboxy terminal end of C4d. A remarkable difference in the predicted secondary structure of C4d arising from one set of four polymorphic residues in a stretch of six residues and another single polymorphic residue suggests a structural basis for the origin of the different chemical reactivities of the C4 isotypes (C4A and C4B) and their serological difference in the expression of Rodgers or Chido blood group antigens. Possible non-covalent membrane attachment sites have been suggested from the hydropathy profile. Comparison of the C4d sequence with human C3, C5 and alpha 2-macroglobulin revealed extended stretches of sequence similarity (between 19 and 38% homology) with the corresponding regions of these proteins.
本文给出了人补体成分C4的C4d片段（长度为380个残基）的完整氨基酸序列。大部分序列是通过对从S-羧甲基化蛋白获得的溴化氰肽和胰蛋白酶肽进行分析确定的。氨基末端88个残基的序列[坎贝尔R.D.、加尼翁J.和波特R.R.（1981年）《生物化学杂志》199卷，359 - 370页]以及C4d的一个106个残基的多态性片段[查克拉瓦蒂D.N.、坎贝尔R.D.和加贡J.（1983年）《欧洲生物化学学会联合会快报》154卷，387 - 390页]得到了延伸。从核苷酸序列预测的氨基酸序列[贝尔特K.T.、卡罗尔M.C.和波特R.R.（1984年）《细胞》36卷，907 - 914页]中获得了一些蛋白质序列分析未提供的重叠部分。目前的蛋白质序列数据为分离C4d的所有溴化氰肽和琥珀酰化胰蛋白酶肽提供了信息。除了先前描述的多态性外，还在第153位（异亮氨酸/丝氨酸）和第154位（谷氨酰胺/丙氨酸）鉴定出另外两组多态性氨基酸残基。已表明主要糖基化位点是位于C4d羧基末端序列 - 天冬酰胺 - 缬氨酸 - 苏氨酸 - 中的一个天冬酰胺残基。由六个残基片段中的一组四个多态性残基和另一个单个多态性残基引起的C4d预测二级结构的显著差异表明了C4同种型（C4A和C4B）不同化学反应性起源及其在表达罗杰斯或奇多血型抗原方面血清学差异的结构基础。从亲水性图谱中推测了可能的非共价膜附着位点。将C4d序列与人C3、C5和α2 - 巨球蛋白进行比较，发现与这些蛋白质的相应区域有延伸的序列相似性片段（同源性在19%至38%之间）。
