BamA forms a translocation channel for polypeptide export across the bacterial outer membrane.
BamA forms a translocation channel for polypeptide export across the bacterial outer membrane.
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DOI：
10.1016/j.molcel.2021.02.023
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发表时间：
2021-05-06
期刊：
影响因子：
16
通讯作者：
Bernstein HD
中科院分区：
文献类型：
--
作者：
Doyle MT;Bernstein HD
β-Barrel装配机将β-Barrel蛋白整合到革兰氏阴性细菌的外膜(OM)中。一个必需的BAM亚单位(BAMA)通过促进其自身的β-Barrel结构域与其客户蛋白之间形成一个杂交桶中间态来催化整合。在这里，我们表明，除了催化β-Barrel蛋白的整合外，BAMA还具有多肽输出通道的功能。通过分子间二硫化物-交联法绘制的体内结构图表明，毒力因子超家族中的一个成员的胞外‘乘客’结构域穿过BAMAβ-Barrel管腔穿过OM。此外，我们证明了在自动转运器β桶中需要一个高度保守的残基来将乘客定位在BAMA内以启动转运，并且在转运过程中乘客稳定了混合桶状态。我们的结果不仅为BAMA建立了一个新的功能，而且统一了BAMA和其他‘Omp85’超家族转运蛋白的不同功能。外膜蛋白的大的可溶性结构域，如自身转运蛋白，是如何分泌到细胞外环境中的，其机制长期以来一直是个谜。多伊尔和伯恩斯坦证明，基本的外膜蛋白BAMA创建了一个独特的通道，实现了这种出口功能。
The β-barrel assembly machine (BAM) integrates β-barrel proteins into the outer membrane (OM) of Gram-negative bacteria. An essential BAM subunit (BamA) catalyzes integration by promoting the formation of a hybrid-barrel intermediate-state between its own β-barrel domain and that of its client proteins. Here we show that in addition to catalyzing the integration of β-barrel proteins, BamA functions as a polypeptide export channel. In vivo structural mapping via intermolecular disulfide-crosslinking showed that the extracellular ‘passenger’ domain of a member of the ‘autotransporter’ superfamily of virulence factors traverses the OM through the BamA β-barrel lumen. Furthermore, we demonstrate that a highly conserved residue within autotransporter β-barrels is required to position the passenger inside BamA to initiate translocation, and that during translocation the passenger stabilizes the hybrid-barrel state. Our results not only establish a new function for BamA, but also unify the divergent functions of BamA and other ‘Omp85’ superfamily transporters. The mechanism by which the large soluble domains of outer membrane proteins such as autotransporters are secreted into the extracellular environment has been a long-standing mystery. Doyle and Bernstein show that the essential outer membrane protein BamA creates a unique channel that fulfils this export function.
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