Structure of human complement C8, a precursor to membrane attack.
Structure of human complement C8, a precursor to membrane attack.
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人类补体C8的结构，这是膜攻击的前体。
DOI：
10.1016/j.jmb.2010.10.031
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发表时间：
2011-01-14
影响因子：
5.6
通讯作者：
Lea SM
中科院分区：
文献类型：
--
作者：
Bubeck D;Roversi P;Donev R;Morgan BP;Llorca O;Lea SM
补体成分C8在膜攻击复合物（MAC）的形成中起着关键作用，MAC是一种重要的抗菌免疫效应物。C8启动膜渗透并协调MAC孔形成。C8亚基的高分辨率结构为C8异源三聚体的功能提供了一些见解;然而，没有结构信息描述亚基间组织如何促进MAC组装。我们用电子显微镜测定了C8的结构，并将C8 α-MACPF（membrane attack complex/perforin）-C8 γ共晶结构和C8 β-MACPF的同源模型拟合到密度中。在这里，我们证明了C8 γ突起和C8 α-MACPF区域在激活时插入膜是可接近的。补体成分C8启动膜攻击复合物的膜穿透，这是一种重要的先天免疫效应物。C8的结构揭示了具有球状突起的核心结构域。将假原子模型与电子显微镜重建结果进行对接表明，C8 γ从C8 α β核心突出，其中预测的C8 α-MACPF的跨膜残基和C8 β-MACPF的一个表面暴露。
Complement component C8 plays a pivotal role in the formation of the membrane attack complex (MAC), an important antibacterial immune effector. C8 initiates membrane penetration and coordinates MAC pore formation. High-resolution structures of C8 subunits have provided some insight into the function of the C8 heterotrimer; however, there is no structural information describing how the intersubunit organization facilitates MAC assembly. We have determined the structure of C8 by electron microscopy and fitted the C8α-MACPF (membrane attack complex/perforin)-C8γ co-crystal structure and a homology model for C8β-MACPF into the density. Here, we demonstrate that both the C8γ protrusion and the C8α-MACPF region that inserts into the membrane upon activation are accessible. ► Complement component C8 initiates membrane penetration of the membrane attack complex, an important innate immune effector. ► The structure of C8 reveals a core domain with a globular protrusion. ► Docking of pseudo-atomic models into the electron microscopy reconstruction indicates that C8γ projects away from the C8αβ core, in which the predicted transmembrane residues of C8α-MACPF and one face of the C8β-MACPF are surface exposed.
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影响因子：
56.9
作者：
Hadders, Michael A.;Beringer, Dennis X.;Gros, Piet
通讯作者：
Gros, Piet
影响因子：
5.6
作者：
Slade, Daniel J.;Lovelace, Leslie L.;Sodetz, James M.
通讯作者：
Sodetz, James M.
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
3
作者：
Pettersen, EF;Goddard, TD;Ferrin, TE
通讯作者：
Ferrin, TE
影响因子：
4.1
作者：
ABRAHA, A;MORGAN, BP;LUZIO, JP
通讯作者：
LUZIO, JP