Incomplete pneumolysin oligomers form membrane pores.
Incomplete pneumolysin oligomers form membrane pores.
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DOI：
10.1098/rsob.140044
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发表时间：
2014-04-23
期刊：
影响因子：
5.8
通讯作者：
Gilbert RJ
中科院分区：
文献类型：
--
作者：
Sonnen AF;Plitzko JM;Gilbert RJ
肺炎溶血素是胆固醇依赖的细胞溶血素(CDC)家族中的一员，该家族以水溶性单体或二聚体的形式产生，结合到靶膜上，并齐聚成约40个亚基、直径约30 nm的大环状组件。然后，这种预孔组装会重新折叠，在脂质双层上打出一个大洞。然而，除了形成大的毛孔外，肺炎溶血素和其他CDC还形成以低电导为特征的较小的病变。由于电子显微镜观察到的是弧形(而不是全环)低聚物，因此假设较小的低聚物解释了较小的功能孔。为了研究是否存在这种情况，我们对模型脂膜上的肺炎溶血素低聚物进行了冷冻电子断层扫描。然后，我们使用亚断层图像分类和平均来确定典型的膜结合的低分辨率结构，并通过寡聚曲线中膜的存在来识别前孔和孔。我们发现了完整(环)和不完全(弧形)齐聚物的预孔和孔形式，得出结论：肺炎溶血素的弧形低聚物组装可以形成孔。由于CDC在进化上与膜攻击复合体/穿孔素家族相关，这些蛋白质家族也形成不同大小的孔，我们的发现也与这类蛋白质相关。
Pneumolysin is a member of the cholesterol-dependent cytolysin (CDC) family of pore-forming proteins that are produced as water-soluble monomers or dimers, bind to target membranes and oligomerize into large ring-shaped assemblies comprising approximately 40 subunits and approximately 30 nm across. This pre-pore assembly then refolds to punch a large hole in the lipid bilayer. However, in addition to forming large pores, pneumolysin and other CDCs form smaller lesions characterized by low electrical conductance. Owing to the observation of arc-like (rather than full-ring) oligomers by electron microscopy, it has been hypothesized that smaller oligomers explain smaller functional pores. To investigate whether this is the case, we performed cryo-electron tomography of pneumolysin oligomers on model lipid membranes. We then used sub-tomogram classification and averaging to determine representative membrane-bound low-resolution structures and identified pre-pores versus pores by the presence of membrane within the oligomeric curve. We found pre-pore and pore forms of both complete (ring) and incomplete (arc) oligomers and conclude that arc-shaped oligomeric assemblies of pneumolysin can form pores. As the CDCs are evolutionarily related to the membrane attack complex/perforin family of proteins, which also form variably sized pores, our findings are of relevance to that class of proteins as well.
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影响因子：
4.8
作者：
Bonev, BB;Gilbert, RJC;Watts, A
通讯作者：
Watts, A
影响因子：
16
作者：
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作者：
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Gros P
DOI：
10.1016/j.bbrc.2008.01.151
发表时间：
2008-04-11
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
15.9
作者：
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通讯作者：
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