Röhrig Ute F, Guidoni Leonardo, Rothlisberger Ursula
Laboratory of Inorganic Chemistry, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland.
Biochemistry. 2002 Sep 3;41(35):10799-809. doi: 10.1021/bi026011h.
We present molecular dynamics simulations of bovine rhodopsin in a membrane mimetic environment based on the recently refined X-ray structure of the pigment. The interactions between the protonated Schiff base and the protein moiety are explored both with the chromophore in the dark-adapted 11-cis and in the photoisomerized all-trans form. Comparison of simulations with Glu181 in different protonation states strongly suggests that this loop residue located close to the 11-cis bond bears a negative charge. Restrained molecular dynamics simulations also provide evidence that the protein tightly confines the absolute conformation of the retinal around the C12-C13 bond to a positive helicity. 11-cis to all-trans isomerization leads to an internally strained chromophore, which relaxes after a few nanoseconds by a switching of the ionone ring to an essentially planar all-trans conformation. This structural transition of the retinal induces in turn significant conformational changes of the protein backbone, especially in helix VI. Our results suggest a possible molecular mechanism for the early steps of intramolecular signal transduction in a prototypical G-protein-coupled receptor.
我们基于最近优化的视紫红质X射线结构，在膜模拟环境中对牛视紫红质进行了分子动力学模拟。研究了质子化席夫碱与蛋白质部分在暗适应的11-顺式发色团以及光异构化的全反式发色团中的相互作用。对处于不同质子化状态的Glu181进行模拟比较，强烈表明位于靠近11-顺式键的这个环残基带有负电荷。受限分子动力学模拟也提供了证据，表明蛋白质将视网膜围绕C12 - C13键的绝对构象紧密限制为正螺旋。11-顺式到全反式的异构化导致发色团内部应变，在几纳秒后通过紫罗兰酮环转变为基本平面的全反式构象而松弛。视网膜的这种结构转变进而诱导蛋白质主链发生显著的构象变化，尤其是在螺旋VI中。我们的结果提示了典型G蛋白偶联受体分子内信号转导早期步骤的一种可能分子机制。
