Darbari Vidya Chandran, Ciccone Jonah, Patel Jagdish Suresh, Islam Barira, Agarwal Pratul K, Haider Shozeb
School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, United Kingdom.
Department of Pharmaceutical and Biological Chemistry, University College London School of Pharmacy, WC1N 1AX London, United Kingdom.
ACS Omega. 2020 Feb 4;5(7):3271-3281. doi: 10.1021/acsomega.9b03313. eCollection 2020 Feb 25.
Type IV secretion systems are large nanomachines assembled across the bacterial cell envelope for effector translocation and conjugation. VirB10 traverses the inner and outer membranes, sensing cellular signals for coordinating the conformational switch for pilus biogenesis and/or secretion. Mutations uncoupling secretion from pilus biogenesis were identified in VirB10 including a gating defect mutation G272R that made VirB10 unresponsive to intracellular ATP, causing unregulated secretion of VirE2 in a contact-independent manner. Comparative long-timescale molecular dynamics of the wild type and G272R mutant of the VirB10 tetradecamer reveals how the G272R mutation locks the oligomer in a rigid conformation by swapping the ionic interactions between the loops from the β-barrel close to the inner leaflet of the outer membrane. This electrostatic switching changes the allosteric communication pathway from the extracellular loop to the base of the barrel, suggesting that the local conformational dynamics in the loops can gate information across VirB10.
IV型分泌系统是横跨细菌细胞膜组装而成的大型纳米机器，用于效应蛋白转运和接合作用。VirB10穿越内膜和外膜，感知细胞信号以协调菌毛生物合成和/或分泌的构象转换。在VirB10中鉴定出了使分泌与菌毛生物合成解偶联的突变，包括一个门控缺陷突变G272R，该突变使VirB10对细胞内ATP无反应，导致VirE2以非接触依赖方式不受调控地分泌。VirB10十四聚体野生型和G272R突变体的比较长时间尺度分子动力学揭示了G272R突变如何通过交换靠近外膜内小叶的β桶环之间的离子相互作用，将寡聚体锁定在刚性构象中。这种静电转换改变了从细胞外环到桶底部的变构通讯途径，表明环中的局部构象动力学可以控制VirB10的信息传递。
