Pöyry Sanja, Cramariuc Oana, Postila Pekka A, Kaszuba Karol, Sarewicz Marcin, Osyczka Artur, Vattulainen Ilpo, Róg Tomasz
Department of Physics, Tampere University of Technology, Tampere, Finland.
Biochim Biophys Acta. 2013 Jun;1827(6):769-78. doi: 10.1016/j.bbabio.2013.03.005. Epub 2013 Mar 23.
The reaction mechanism of the cytochrome (cyt) bc1 complex relies on proton and electron transfer to/from the substrate quinone/quinol, which in turn generate a proton gradient across the mitochondrial membrane. Cardiolipin (CL) have been suggested to play an important role in cyt bc1 function by both ensuring the structural integrity of the protein complex and also by taking part in the proton uptake. Yet, the atom-scale understanding of these highly charged four-tail lipids in the cyt bc1 function has remained quite unclear. We consider this issue through atomistic molecular dynamics simulations that are applied to the entire cyt bc1 dimer of the purple photosynthetic bacterium Rhodobacter capsulatus embedded in a lipid bilayer. We find CLs to spontaneously diffuse to the dimer interface to the immediate vicinity of the higher potential heme b groups of the complex's catalytic Qi-sites. This observation is in full agreement with crystallographic studies of the complex, and supports the view that CLs are key players in the proton uptake. The simulation results also allow us to present a refined picture for the dimer arrangement in the cyt bc1 complex, the novelty of our work being the description of the role of the surrounding lipid environment: in addition to the specific CL-protein interactions, we observe the protein domains on the positive side of the membrane to settle against the lipids. Altogether, the simulations discussed in this article provide novel views into the dynamics of cyt bc1 with lipids, complementing previous experimental findings.
细胞色素（cyt）bc1复合物的反应机制依赖于质子和电子与底物醌/醌醇之间的转移，进而在线粒体内膜上产生质子梯度。心磷脂（CL）被认为在cyt bc1功能中起重要作用，既确保蛋白质复合物的结构完整性，又参与质子摄取。然而，对于这些在cyt bc1功能中高度带电的四尾脂质的原子尺度理解仍相当不清楚。我们通过原子分子动力学模拟来考虑这个问题，该模拟应用于嵌入脂质双层中的紫色光合细菌荚膜红细菌的整个cyt bc1二聚体。我们发现CL会自发扩散到二聚体界面，到达复合物催化Qi位点中较高电位血红素b基团的紧邻区域。这一观察结果与该复合物的晶体学研究完全一致，并支持CL是质子摄取关键参与者的观点。模拟结果还使我们能够呈现cyt bc1复合物中二聚体排列的精细图景，我们工作的新颖之处在于描述了周围脂质环境的作用：除了特定的CL - 蛋白质相互作用外，我们观察到膜正侧的蛋白质结构域靠脂质沉降。总之，本文讨论的模拟为cyt bc1与脂质的动力学提供了新的观点，补充了先前的实验结果。
