整合膜蛋白主要分为两个基本的大类：α-螺旋膜蛋白和β-桶状膜蛋白。β-桶状膜蛋白主要分布于线粒体、叶绿体以及革兰氏阴性细菌的外膜内，行使许多重要的生物学功能。在革兰氏阴性细菌中，细菌外膜内的各种新生β-桶状膜蛋白由一个定位于外膜的BAM复合体负责插膜生成。因此，BAM复合体为革兰氏阴性细菌的存活所必需，也是重要的新型抗生素靶点。完整的BAM复合体由BamA、BamB、BamC、BamD和BamE五个亚基组成，分子量约为200 KD。但BAM复合体如何组装以及如何行使插膜功能尚不清楚。

2月22日，Nature 杂志子刊Nature Structural & Molecular Biology 在线发表了中国科学院生物物理研究所黄亿华课题组的研究论文Structure of the BAM complex and its implications for biogenesis of outer-membrane proteins。该项研究首次解析了BAM 蛋白复合体完整的晶体结构，发现其形成一个类似于“帽子”状的结构：BamA的跨膜区由16条β-链围成，形成“帽冠”镶嵌于外膜内，而组成BamA的5个pOTRA（polypeptide transport-associated）结构域则在周质内中和四个脂蛋白BamB，BamC， BamD及BamE相互结合形成“帽沿”。这种构象能够为分子伴侣——新生β-桶状膜蛋白底物复合体提供结合位点。结构分析和功能实验进一步揭示了BAM复合体中各个组分之间的相互作用以及潜在的底物插入外膜出口，初步揭示了BAM复合体介导的细菌外膜内新生β-桶状膜蛋白的插膜生成机理。

该研究工作得到了科技部“973”计划、国家自然科学基金以及中国科学院战略性先导科技专项（B类）的资助。

图示：BAM复合体的整体结构

原文摘要：

Structure of the BAM complex and its implications for biogenesis of outer-membrane proteins

In Gram-negative bacteria, the assembly of β-barrel outer-membrane proteins (OMps) requires the β-barrel–assembly machinery (BAM) complex. We determined the crystal structure of the 200-kDa BAM complex from Escherichia coli at 3.55-Å resolution. The structure revealed that the BAM complex assembles into a hat-like shape, in which the BamA β-barrel domain forms the hat"s crown embedded in the outer membrane, and its five polypeptide transport–associated (pOTRA) domains interact with the four lipoproteins BamB, BamC, BamD and BamE, thus forming the hat"s brim in the periplasm. The assembly of the BAM complex creates a ring-like apparatus beneath the BamA β-barrel in the periplasm and a potential substrate-exit pore located at the outer membrane–periplasm interface. The complex structure suggests that the chaperone-bound OMp substrates may feed into the chamber of the ring-like apparatus and insert into the outer membrane via the potential substrate-exit pore in an energy-independent manner.