Ficici Emel, Jeong Daun, Andricioaei Ioan
Department of Chemistry, University of California, Irvine, Irvine, California.
Department of Chemistry, University of California, Irvine, Irvine, California.
Biophys J. 2017 Jun 20;112(12):2520-2528. doi: 10.1016/j.bpj.2017.04.034.
SecDF is an important component of the Sec protein translocation machinery embedded in the bacterial membrane, which is associated with many functions, such as stabilizing other Sec translocon components within the membrane, maintaining the transmembrane (TM) potential, and facilitating the ATP-independent stage of the translocation mechanism. Related studies suggest that SecDF undergoes functionally important conformational changes that involve mainly its P1-head domain and that these changes are coupled with the proton motive force (Δp). However, there still is not a clear understanding of how SecDF functions, its exact role in the translocation machinery, and how its function is related to Δp. Here, using all-atom molecular dynamics simulations combined with umbrella sampling, we study the P1-head conformational change and how it is coupled to the proton motive force. We report potentials of mean force along a root-mean-square-distance-based reaction coordinate obtained in the presence and absence of the TM electrical potential. Our results show that the interaction of the P1 domain dipole moment with the TM electrical field considerably lowers the free-energy barrier in the direction of F-form to I-form transition.
SecDF是嵌入细菌膜中的Sec蛋白转运机制的重要组成部分,它与许多功能相关,如稳定膜内的其他Sec转运体成分、维持跨膜(TM)电位以及促进转运机制中不依赖ATP的阶段。相关研究表明,SecDF经历了功能上重要的构象变化,主要涉及其P1头部结构域,并且这些变化与质子动力(Δp)相关。然而,对于SecDF如何发挥功能、其在转运机制中的确切作用以及其功能如何与Δp相关,仍没有清晰的认识。在这里,我们使用全原子分子动力学模拟结合伞形采样,研究P1头部的构象变化及其与质子动力的耦合方式。我们报告了在存在和不存在TM电势的情况下,沿着基于均方根距离的反应坐标获得的平均力势。我们的结果表明,P1结构域偶极矩与TM电场的相互作用大大降低了F型向I型转变方向的自由能垒。