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 alpha subunit and C9.
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 alpha subunit and C9.
复制标题
人补体蛋白 C8 β 亚基的互补 DNA 和衍生氨基酸序列：鉴定与 α 亚基和 C9 的密切结构和祖先关系。
DOI：
10.1021/bi00386a047
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发表时间：
1987
期刊：
影响因子：
2.9
通讯作者：
Sodetz,JM
中科院分区：
文献类型：
--
作者：
Howard,OM;Rao,AG;Sodetz,JM
南卡罗来纳州大学化学系和医学院，哥伦比亚，南卡罗来纳州29208接收于1987年1月30日;修订于1987年3月5日摘要：从人肝cDNA文库中分离出编码补体第八组分（C8）f3亚基（A/j.64000）的cDNA克隆。该克隆具有1.95个碱基（kb）的cDNA插入片段，并含有完整的β序列[1608个碱基对（bp）]。对从肝癌细胞系HepG 2分离的总细胞RNA的分析显示β的mRNA为约2.5kb。这与C8的α亚基的信息大小相似，并证实了α和β的不同mRNA的存在。这一发现支持了遗传学证据，即α和β在不同的基因座编码。衍生的氨基酸序列的分析揭示了几个膜表面寻求段，可能有助于在补体介导的细胞溶解过程中与靶膜的相互作用。碳水化合物组成的测定表明有1或2个天冬酰胺连接的寡糖链，但没有O-连接的寡糖链。比较（3）序列与前一篇论文[Rao，A. G.，霍华德，O. M. Z.，Ng，S. C.的方法，怀特海，A.美国，Colten，H. R. & Sodetz，J. M.（1987）Biochemistry（在此问题上的前一篇论文）]和人类C9的结果揭示了所有三种蛋白质之间惊人的同源性。对于β和α，基于同一性的总体同源性为33%，当允许保守取代时为53%。对于f3和C9，该值分别为26%和47%。所有这三个有一个大的内部结构域，几乎是半胱氨酸自由和N-和C-末端是半胱氨酸丰富的和同源的低密度脂蛋白受体重复序列和表皮生长因子类型的序列，分别。整体同源性和相似性的大小和结构组织是一个密切的祖先关系的指示。它的结论是，a，/3，和C9是一个家庭的成员的结构相关的蛋白质，能够相互作用，以产生一个亲水性的两亲性的过渡和膜协会。
Department of Chemistry and School of Medicine, University of South Carolina, Columbia, South Carolina 29208 Received January 30, 1987; Revised Manuscript Received March 5, 1987 abstract: A cDNA clone encoding the f3 subunit (A/j. 64000) 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/3 sequence [1608 base pairs (bp)]. Analysis of total cellular RNA isolated from the hepatoma cell line HepG2 revealed the mRNA for (3 to be~ 2.5 kb. This is similar to the message size for the a subunit of C8 and confirms the existence of different mRNAs for a and (3. This finding supports genetic evidence that a and/3 are encoded at different loci. Analysis of the derived amino acid sequence revealed several membrane surface seeking segments that may facilitate/3 interaction with target membranes during complement-mediated cytolysis. Determination of the carbohydrate composition indicated 1 or 2 asparagine-linked but no O-linked oligosaccharidechains. Comparison of the (3 sequence to that reported for a in the preceding paper [Rao, A. G., Howard, O. M. Z., Ng, S. C., Whitehead, A. S., Colten, H. R. & Sodetz, J. M.(1987) Biochemistry (preceding paper in this issue)] andto that of humanC9 revealed a striking homology between all three proteins. For/3 and a, the overall homology is 33% on the basis of identity and 53% when conserved substitutions are allowed. For/3 and C9, the values are 26% and 47%, 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 a,/3, 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.