The multifunctional role of C3: structural analysis of its interactions with physiological ligands.
The multifunctional role of C3: structural analysis of its interactions with physiological ligands.
复制标题
C3 的多功能作用：其与生理配体相互作用的结构分析。
DOI：
10.1016/0161-5890(86)90157-4
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发表时间：
1986
影响因子：
3.6
通讯作者：
Müller-Eberhard,HJ
中科院分区：
文献类型：
--
作者：
Lambris,JD;Müller-Eberhard,HJ
在迄今为止已识别的 20 种不同的补体蛋白中，C3 可能是最通用的，因为它在经典途径和替代途径中都发挥着关键作用（有关综述，请参见 Muher-Eberhard，1975；Porter 和 Reid，1979）。因此，C3的结构和多种功能一直是深入研究的课题。C3[分子量(mol.wt)190,000]是血清中最丰富的补体蛋白(I.2m&ml)，由两条多肽链3:和/_I组成，通过二硫键和非共价力连接。通过经典或旁路途径 C3 转化酶在 a 链第 77 和 78 位之间的 Arg-Ser 肽键处裂解 C3，生成 C3a，即 9000 mol。具有过敏毒素活性的wt片段和C3b（图1）。 C3b 片段可以在短时间内通过不稳定的结合位点（Miller-Eberhard 等，1966；Law 等，1979；Tack 等，1980）与细胞表面、复合多糖或免疫聚集体共价结合。与天然 C3 不同，C3b 片段表达多个结合位点，包括 C5 位点（Vogt 等人，1978）、备解素 (P)（Chapitis 和 Lepow，1976；Schreiber 等人，1975）、H 因子位点（Whaley 和 Ruddy，1976；Weiler 等人，1976）、I3 因子位点（Fearon 等人，1973； Brade等人，1973)、因子I(Vogt等人，1977)和CR1，C3b受体(Nelson，1953：Gigli和Nelson，1968)。 C3b 上的结合位点的接合具有以下效果。结合的因子 B 变得容易受到因子 D 的切割和激活。结合的 P 可以稳定所得的 C3 转化酶，结合的 C5 可以被 C3b 激活。 Bb 或 C4b。 2a. H 因子的结合加速了 C3 转化酶的衰变解离，并通过因子 I 调节 C3b 的酶促降解。靶细胞结合的 C3b 与吞噬细胞上的 CR1 结合会引起细胞粘附，从而可能诱导摄入或细胞外杀伤。结合的 C3b 表现出的许多活性是
Of the 20 distinct complement proteins recognized to date, C3 is probably the most versatile because of its pivotal role in both the classical and alternative pathways (for review, see Muher-Eberhard, 1975; Porter and Reid, 1979). Therefore, the structure and multiple functions of C3 have been the subject of intensive study.C3 [molecular weight (mol. wt) 190,000], the most abundant complement protein in serum (I. 2 m&ml), consists of two polypeptide chains, 3: and/_I, linked by disulfide bonds and non-covalent forces. Cleavage of C3 by the classical or alternative pathway C3 convertases at an Arg-Ser peptide bond between positions 77 and 78 of the a chain generates C3a, a 9000 mol. wt fragment with anaphylatoxin activity, and C3b (Fig. 1). The C3b fragment can, for a brief period, bind covalently via a labile binding site (Miller-Eberhard et al., 1966; Law et al., 1979; Tack et al., 1980) to cell surfaces, complex polysaccharides or immune aggregates. Unlike native C3, and C3b fragment expresses multiple binding sites, including sites for C5 (Vogt et al., 1978), properdin (P)(Chapitis and Lepow, 1976; Schreiber et al., 1975), factor H (Whaley and Ruddy. 1976; Weiler et al., 1976), factor I3 (Fearon et al., 1973; Brade et al., 1973), factor I (Vogt et al., 1977) and CRl, the C3b receptor (Nelson, 1953: Gigli and Nelson, 1968). Engagement of the binding sites on C3b has the following effects. Bound factor B becomes susceptible to cleavage and activation by factor D. Bound P stabilizes the resulting C3 convertase, bound C5 can be activated by C3b. Bb or C4b. 2a. Binding of factor H accelerates the decay-dissociation of the C3 convertase and modulates C3b for enzymatic degradation by factor I. Engagement of target cell-bound C3b with the CR1 on phagocytic cells causes cell adhesion, which may induce ingestion or extracellular killing. Many of the activities exhibited by bound C3b are