Analysis of the specific association of the eighth and ninth components of human complement: identification of a direct role for the alpha subunit of C8.
Analysis of the specific association of the eighth and ninth components of human complement: identification of a direct role for the alpha subunit of C8.
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人类补体第八和第九成分的特异性关联分析：鉴定 C8 α 亚基的直接作用。
DOI：
10.1021/bi00338a018
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发表时间：
1985
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：
Stewart,JL;Sodetz,JM
南卡罗来纳大学化学系和医学院，1985年1月17日收到的摘要：通过分离C8的非共价结合的-y和？亚基并确定它们各自与C9的亲和力，研究了溶液中C8和C9之间的物理结合的基础。结果表明，只有Ay与C9结合，这种结合虽然可逆，但在接近各组分的等摩尔比时是完全的。进一步用纯化的α或y进行的实验表明，只有a能够与C9形成稳定的络合物。虽然这种相互作用的强度依赖于盐的浓度，但在生理离子强度的缓冲液和人血清中观察到了相互作用。这些结果表明，C8上负责与C9相互作用的结构域完全位于a内。在相关实验中，向(Ay+C9)或(a+C9)的预先形成的二聚体中加入？可使该亚基完全结合。这些特殊的结果表明，在a上有两个物理上不同的位点，分别介导a与ç和与C9的联系。此外，占据一个部位并不损害另一个部位的相互作用(补体介导的细胞膜溶解是C5b、C6、Cl、C8和C9之间特定相互作用的结果(Bhakdi&Tranum-Jensen，1983；Podack&Tschopp，1984)。通过C5b的形成启动细胞溶解复合体在靶膜上的组装，并以顺序的方式进行
Department of Chemistry and School of Medicine, University of South Carolina, Columbia, South Carolina 29208 Received January 17, 1985 abstract: The basis for the physical association between C8 and C9 in solution was examined by isolating the noncovalently associated-y and ß subunits of C8 and determining their respective affinities for C9. Results indicate that only ay associates with C9 and this association, though reversible, is complete at near equimolar ratios of each component. Further experimentsusing purified a or y revealed that only a was capable of forming a stable complex with C9. Although the strength of this interaction was dependent on salt concentration, association was observed in buffer of physiological ionic strength and in human serum. These results establish that the domain on C8 responsible for interaction with C9 is located entirelywithin a. In related experiments, addition of ß to preformed dimers of either (ay+ C9) or (a+ C9) resulted in complete association of this subunit. These particular results indicate that there are two physically distinct sites on a that separately mediateassociation of a with ß and with C9. Furthermore, occupation of one site does not impair interaction at the other.(Complement-mediated lysis of cell membranes occurs as a result of specific interaction between C5b, C6, Cl, C8, and C9 (Bhakdi & Tranum-Jensen, 1983; Podack & Tschopp, 1984). Assembly of the cytolytic complex on target mem-branes is initiated by formation of C5b and proceeds in the sequential manner