Parr Rebecca J, Santin Yoann G, Ratkevičiūte Giedrė, Caulton Simon G, Radford Paul, Gurvič Dominik, Jenkins Matthew, Doyle Matthew T, Mead Liam, Silale Augustinas, van den Berg Bert, Knowles Timothy J, Sockett R Elizabeth, Stansfeld Phillip J, Laloux Géraldine, Lovering Andrew L
School of Biosciences, University of Birmingham, Birmingham, UK.
MPL, Diamond Synchrotron, Didcot, UK.
Nat Commun. 2025 Jul 5;16(1):6213. doi: 10.1038/s41467-025-61633-0.
Outer membrane proteins (OMPs) define the surface biology of Gram-negative bacteria, with roles in adhesion, transport, catalysis and signalling. Specifically, porin beta-barrels are common diffusion channels, predominantly monomeric/trimeric in nature. Here we show that the major OMP of the bacterial predator Bdellovibrio bacteriovorus, PopA, differs from this architecture, forming a pentameric porin-like superstructure. Our X-ray and cryo-EM structures reveal a bowl-shape composite outer β-wall, which houses a central chamber that encloses a section of the lipid bilayer. We demonstrate that PopA, reported to insert into prey inner membrane, causes defects when directed into Escherichia coli membranes. We discover widespread PopA homologues, including likely tetramers and hexamers, that retain the lipid chamber; a similar chamber is formed by an unrelated smaller closed-barrel family, implicating this as a general feature. Our work thus defines oligomeric OMP superfamilies, whose deviation from prior structures requires us to revisit existing membrane-interaction motifs and folding models.
外膜蛋白（OMPs）决定了革兰氏阴性菌的表面生物学特性，在黏附、运输、催化和信号传导中发挥作用。具体而言，孔蛋白β桶是常见的扩散通道，本质上主要为单体/三聚体。在这里，我们表明细菌捕食者食菌蛭弧菌的主要外膜蛋白PopA与这种结构不同，形成了一种五聚体孔蛋白样超结构。我们的X射线和冷冻电镜结构揭示了一个碗状复合外β壁，其包含一个包围脂质双层一部分的中央腔室。我们证明，据报道可插入猎物内膜的PopA，当被导向大肠杆菌膜时会导致缺陷。我们发现了广泛存在的PopA同源物，包括可能的四聚体和六聚体，它们保留了脂质腔室；一个不相关的较小封闭桶家族也形成了类似的腔室，这表明这是一个普遍特征。因此，我们的工作定义了寡聚外膜蛋白超家族，其与先前结构的偏差要求我们重新审视现有的膜相互作用基序和折叠模型。
