Membrane attack complex of complement: distribution of subunits between the hydrocarbon phase of target membranes and water.

Membrane attack complex of complement: distribution of subunits between the hydrocarbon phase of target membranes and water.
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DOI:
10.1073/pnas.78.7.4544
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发表时间:
1981-07
影响因子:
11.1
通讯作者:
E. Podack;W. Stoffel;A. F. Esser;H. Müller-Eberhard
E. Podack;W. Stoffel;A. F. Esser;H. Müller-Eberhard
中科院分区:
综合性期刊1区
文献类型:
--
作者:
E. Podack;W. Stoffel;A. F. Esser;H. Müller-Eberhard

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补体对膜的破坏受膜攻击复合物(MAC)的影响,所述膜攻击复合物是补体蛋白C5b、C6、C7、C8和C9的融合产物的二聚体。磷脂双层囊泡被用作MAC及其中间复合物的靶膜。这些膜结合的复合物的亚基进行了探讨,其相对暴露于烃相的脂双层和水周围的脂囊泡。暴露于水相的蛋白质用125I标记;暴露于烃相的蛋白质通过使用氚化叠氮基磷脂和照射来标记。对膜结合MAC的分析表明,亚基C5b、C8 β和C9暴露于水相。亚基C8 α-γ和C9主要与烃相接触。C6和C7几乎不暴露于任一相,表明这些蛋白质在MAC内不可接近。对中间复合物的分析表明,C5b是膜结合的C5b-7中暴露于水最多的亚基,C5b和C8 β是C5b-8中暴露于水的亚基。亚基暴露于烃相的脂质双层在MAC组装过程中发生变化。而C5b-7的所有三个亚基都携带磷脂光标记;大部分标记结合到C5b-8中的C8亚基和MAC中的C9。据认为,与膜的烃核心的接触是由C5b-7通过其每个亚基,由C5b-8通过C8,和由MAC通过C8,特别是C9建立的。
Membrane destruction by complement is effected by the membrane attack complex (MAC) which is the dimer of a fusion product of the complement proteins C5b, C6, C7, C8, and C9. Phospholipid bilayer vesicles were used as target membranes for the MAC and its intermediate complexes. The subunits of these membrane-bound complexes were explored as to their relative exposure to the hydrocarbon phase of the lipid bilayer and to water surrounding the lipid vesicles. Protein exposed to the aqueous phase was labeled with 125I; protein exposed to the hydrocarbon phase was labeled by using tritiated azido phospholipids and irradiation. Analysis of the membrane-bound MAC showed that subunits C5b, C8 beta, and C9 were exposed to the aqueous phase. The subunits C8 alpha-gamma and C9 were primarily in contact with the hydrocarbon phase. C6 and C7 were little exposed to either phase, suggesting that these proteins are inaccessible within the MAC. Analysis of the intermediate complexes showed that C5b was the subunit most exposed to water in membrane-bound C5b-7, and C5b and C8 beta were the water-exposed subunits in C5b-8. Subunit exposure to the hydrocarbon phase of the lipid bilayer changed during MAC assembly. Whereas all three subunits of C5b-7 carried the phospholipid photolabel; most of the label was bound to the C8 subunit in C5b-8 and to C9 in the MAC. It is proposed that contact with the hydrocarbon core of membranes is established by C5b-7 through each of its subunits, by C5b-8 through C8, and by the MAC through C8 and, particularly, C9.