Yu Daqi, Ma Xiaomin, Tu Yuhai, Lai Luhua
1] BNLMS, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing. 100871, China [2] Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing. 100871, China.
Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing. 100871, China.
Sci Rep. 2015 Mar 2;5:8640. doi: 10.1038/srep08640.
Bacterial chemotaxis signaling is triggered by binding of chemo-effectors to the membrane-bound chemoreceptor dimers. Though much is known about the structure of the chemoreceptors, details of the receptor dynamics and their effects on signaling are still unclear. Here, by using molecular dynamics simulations and principle component analysis, we study the dynamics of the periplasmic domain of aspartate chemoreceptor Tar dimer and its conformational changes when binding to different ligands (attractant, antagonist, and two attractant molecules). We found two dominant components (modes) in the receptor dynamics: a relative rotation of the two Tar monomers and a piston-like up-and-down sliding movement of the α4 helix. These two modes are highly correlated. Binding of one attractant molecule to the Tar dimer induced both significant piston-like downward movements of the α4 helix and strong relative rotations of the two Tar monomers, while binding of an antagonist or the symmetric binding of two attractant molecules to a Tar dimer suppresses both modes. The anti-symmetric effects of the relative rotation mode also explained the negative cooperativity between the two binding pockets. Our results suggest a mechanism of coupled rotation and piston-like motion for bacterial chemoreceptor signaling.
细菌趋化信号传导是由化学效应物与膜结合的化学感受器二聚体结合引发的。尽管人们对化学感受器的结构了解很多，但受体动力学的细节及其对信号传导的影响仍不清楚。在这里，我们通过分子动力学模拟和主成分分析，研究了天冬氨酸化学感受器Tar二聚体周质结构域的动力学及其与不同配体（引诱剂、拮抗剂和两个引诱剂分子）结合时的构象变化。我们在受体动力学中发现了两个主要成分（模式）：两个Tar单体的相对旋转和α4螺旋的活塞式上下滑动运动。这两种模式高度相关。一个引诱剂分子与Tar二聚体结合会引起α4螺旋显著的活塞式向下运动以及两个Tar单体的强烈相对旋转，而拮抗剂的结合或两个引诱剂分子与Tar二聚体的对称结合则会抑制这两种模式。相对旋转模式的反对称效应也解释了两个结合口袋之间的负协同性。我们的结果提出了一种细菌化学感受器信号传导的耦合旋转和活塞式运动机制。
