Celia Herve, Botos Istvan, Ghirlando Rodolfo, Duché Denis, Beach Bridgette M, Lloubes Roland, Buchanan Susan K
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Laboratoire d'Ingénierie des Systèmes Macromoléculaires, UMR7255 CNRS/Aix-Marseille Université, Institut de Microbiologie de la Méditerranée, 13402, Marseille, France.
Nat Commun. 2025 Jul 1;16(1):5506. doi: 10.1038/s41467-025-61286-z.
The Ton and Tol motor proteins use the proton gradient at the inner membrane of Gram-negative bacteria as an energy source. The generated force is transmitted through the periplasmic space to protein components associated with the outer membrane, either to maintain the outer membrane integrity for the Tol system, or to allow essential nutrients to enter the cell for Ton. We have solved the high-resolution structures of the E. coli TonB-ExbB-ExbD and TolA-TolQ-TolR complexes, revealing the inner membrane embedded engine parts of the Ton and Tol systems, and showing how TonB and TolA interact with the ExbBD and TolQR subcomplexes. Structural similarities between the two motor complexes suggest a common mechanism for the opening of the proton channel and the propagation of the proton motive force into movement of the TonB and TolA subunits. Because TonB and TolA bind at preferential ExbB or TolQ subunits, we propose a new mechanism of assembly of TonB and TolA with their respective ExbBD and TolQR subcomplexes and discuss its impact on the mechanism of action for the Ton and Tol systems.
托恩（Ton）和托尔（Tol）运动蛋白利用革兰氏阴性菌内膜上的质子梯度作为能量来源。产生的力通过周质空间传递到与外膜相关的蛋白质组分，对于托尔系统而言是维持外膜完整性，对于托恩系统则是使必需营养物质进入细胞。我们解析了大肠杆菌托恩B-外排蛋白B-外排蛋白D（TonB-ExbB-ExbD）和托尔A-托尔Q-托尔R（TolA-TolQ-TolR）复合物的高分辨率结构，揭示了托恩和托尔系统嵌入内膜的发动机部件，并展示了托恩B和托尔A如何与外排蛋白BD和托尔QR亚复合物相互作用。这两种运动复合物之间的结构相似性表明，质子通道开放以及质子动力转化为托恩B和托尔A亚基运动存在共同机制。由于托恩B和托尔A优先结合在外排蛋白B或托尔Q亚基上，我们提出了托恩B和托尔A与其各自的外排蛋白BD和托尔QR亚复合物组装的新机制，并讨论了其对托恩和托尔系统作用机制的影响。
