Khalid Syma, Bond Peter J, Carpenter Timothy, Sansom Mark S P
Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
Biochim Biophys Acta. 2008 Sep;1778(9):1871-80. doi: 10.1016/j.bbamem.2007.05.024. Epub 2007 Jun 2.
Outer membrane proteins (OMPs) of Gram-negative bacteria have a variety of functions including passive transport, active transport, catalysis, pathogenesis and signal transduction. Whilst the structures of approximately 25 OMPs are currently known, there is relatively little known about their dynamics in different environments. The outer membrane protein, OmpA from Escherichia coli has been studied extensively in different environments both experimentally and computationally, and thus provides an ideal test case for the study of the dynamics and environmental interactions of outer membrane proteins. We review molecular dynamics simulations of OmpA and its homologues in a variety of different environments and discuss possible mechanisms of pore gating. The transmembrane domain of E. coli OmpA shows subtle differences in dynamics and interactions between a detergent micelle and a lipid bilayer environment. Simulations of the crystallographic unit cell reveal a micelle-like network of detergent molecules interacting with the protein monomers. Simulation and modelling studies emphasise the role of an electrostatic-switch mechanism in the pore-gating mechanism. Simulation studies have been extended to comparative models of OmpA homologues from Pseudomonas aeruginosa (OprF) and Pasteurella multocida (PmOmpA), the latter model including the periplasmic C-terminal domain.
革兰氏阴性菌的外膜蛋白（OMPs）具有多种功能，包括被动运输、主动运输、催化作用、致病机制和信号转导。虽然目前已知约25种外膜蛋白的结构，但对于它们在不同环境中的动力学了解相对较少。来自大肠杆菌的外膜蛋白OmpA已在不同环境中通过实验和计算进行了广泛研究，因此为研究外膜蛋白的动力学和环境相互作用提供了一个理想的测试案例。我们综述了OmpA及其同源物在各种不同环境中的分子动力学模拟，并讨论了孔道门控的可能机制。大肠杆菌OmpA的跨膜结构域在去污剂胶束和脂质双层环境中的动力学和相互作用表现出细微差异。晶体学晶胞的模拟揭示了与蛋白质单体相互作用的去污剂分子的胶束样网络。模拟和建模研究强调了静电开关机制在孔道门控机制中的作用。模拟研究已扩展到铜绿假单胞菌（OprF）和多杀巴斯德菌（PmOmpA）的OmpA同源物的比较模型，后者模型包括周质C末端结构域。
