Structure of C8α-MACPF reveals mechanism of membrane attack in complement immune defense
Structure of C8α-MACPF reveals mechanism of membrane attack in complement immune defense
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DOI：
10.1126/science.1147103
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发表时间：
2007-09-14
期刊：
影响因子：
56.9
通讯作者：
Gros, Piet
中科院分区：
文献类型：
--
作者：
Hadders, Michael A.;Beringer, Dennis X.;Gros, Piet
膜攻击对于哺乳动物抵抗入侵微生物和感染的宿主细胞的免疫防御是重要的。补体膜攻击复合物（MAC）的蛋白质和穿孔蛋白共有共同的MACPF结构域，其负责膜插入和孔形成。我们在2.5埃分辨率下确定了补体成分C8 α的MACPF结构域的晶体结构，并表明它在结构上与细菌、成孔、胆固醇依赖性溶细胞素同源。该结构显示两个区域（在细菌溶细胞素中）重新折叠成跨膜β发夹，形成桶孔的衬里。局部疏水性解释了为什么C8 α是第一个插入膜的补体蛋白。MACPF结构域的大小与已知的C9孔径一致。这些数据表明，这些哺乳动物和细菌的溶细胞蛋白有着共同的膜插入机制。
Membrane attack is important for mammalian immune defense against invading microorganisms and infected host cells. Proteins of the complement membrane attack complex (MAC) and the protein perforin share a common MACPF domain that is responsible for membrane insertion and pore formation. We determined the crystal structure of the MACPF domain of complement component C8 alpha at 2.5 angstrom resolution and show that it is structurally homologous to the bacterial, pore-forming, cholesterol-dependent cytolysins. The structure displays two regions that (in the bacterial cytolysins) refold into transmembrane beta hairpins, forming the lining of a barrel pore. Local hydrophobicity explains why C8 alpha is the first complement protein to insert into the membrane. The size of the MACPF domain is consistent with known C9 pore sizes. These data imply that these mammalian and bacterial cytolytic proteins share a common mechanism of membrane insertion.