视紫红质的光激活：固态 NMR 距离约束指导下的分子动力学模拟的新见解。
Light activation of rhodopsin: insights from molecular dynamics simulations guided by solid-state NMR distance restraints.
机构信息
Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, USA.
出版信息
J Mol Biol. 2010 Feb 26;396(3):510-27. doi: 10.1016/j.jmb.2009.12.003. Epub 2009 Dec 11.
Abstract
Structural restraints provided by solid-state NMR measurements of the metarhodopsin II intermediate are combined with molecular dynamics simulations to help visualize structural changes in the light activation of rhodopsin. Since the timescale for the formation of the metarhodopsin II intermediate (>1 ms) is beyond that readily accessible by molecular dynamics, we use NMR distance restraints derived from 13C dipolar recoupling measurements to guide the simulations. The simulations yield a working model for how photoisomerization of the 11-cis retinylidene chromophore bound within the interior of rhodopsin is coupled to transmembrane helix motion and receptor activation. The mechanism of activation that emerges is that multiple switches on the extracellular (or intradiscal) side of rhodopsin trigger structural changes that converge to disrupt the ionic lock between helices H3 and H6 on the intracellular side of the receptor.
摘要
固态 NMR 测量对视紫红质 II 中间态的结构限制与分子动力学模拟相结合，有助于可视化视紫红质光激活过程中的结构变化。由于形成视紫红质 II 中间态的时间尺度（>1 ms）超出了分子动力学的可及范围，我们使用来自 13C 偶极重聚测量的 NMR 距离限制来指导模拟。模拟产生了一个工作模型，说明结合在视紫红质内部的 11-顺式视黄醛发色团的光异构化如何与跨膜螺旋运动和受体激活偶联。出现的激活机制是，视紫红质细胞外（或盘内）侧的多个开关触发结构变化，这些变化汇聚在一起破坏受体细胞内侧的 H3 和 H6 螺旋之间的离子锁。
相似文献
1
Light activation of rhodopsin: insights from molecular dynamics simulations guided by solid-state NMR distance restraints.视紫红质的光激活：固态 NMR 距离约束指导下的分子动力学模拟的新见解。
J Mol Biol. 2010 Feb 26;396(3):510-27. doi: 10.1016/j.jmb.2009.12.003. Epub 2009 Dec 11.
2
Location of Trp265 in metarhodopsin II: implications for the activation mechanism of the visual receptor rhodopsin.视紫红质II中色氨酸265的位置：对视紫红质视觉受体激活机制的影响。
J Mol Biol. 2006 Mar 17;357(1):163-72. doi: 10.1016/j.jmb.2005.12.046. Epub 2006 Jan 3.
3
Structural transitions of transmembrane helix 6 in the formation of metarhodopsin I.跨膜螺旋 6 的结构转变在视紫红质 I 的形成中的作用。
J Phys Chem B. 2012 Sep 6;116(35):10477-89. doi: 10.1021/jp3019183. Epub 2012 May 17.
4
Helix movement is coupled to displacement of the second extracellular loop in rhodopsin activation.在视紫红质激活过程中，螺旋运动与第二个细胞外环的位移相关联。
Nat Struct Mol Biol. 2009 Feb;16(2):168-75. doi: 10.1038/nsmb.1549. Epub 2009 Feb 1.
5
Retinal dynamics during light activation of rhodopsin revealed by solid-state NMR spectroscopy.固态核磁共振光谱揭示视紫红质光激活过程中的视网膜动力学。
Biochim Biophys Acta. 2010 Feb;1798(2):177-93. doi: 10.1016/j.bbamem.2009.08.013. Epub 2009 Aug 28.
6
Coupling of retinal isomerization to the activation of rhodopsin.视网膜异构化与视紫红质激活的偶联。
Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10048-53. doi: 10.1073/pnas.0402848101. Epub 2004 Jun 25.
7
Retinal orientation and interactions in rhodopsin reveal a two-stage trigger mechanism for activation.视紫红质的视网膜取向和相互作用揭示了激活的两阶段触发机制。
Nat Commun. 2016 Sep 2;7:12683. doi: 10.1038/ncomms12683.
8
Highly conserved tyrosine stabilizes the active state of rhodopsin.高度保守的酪氨酸稳定了视紫红质的激活态。
Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19861-6. doi: 10.1073/pnas.1009405107. Epub 2010 Nov 1.
9
Retinylidene ligand structure in bovine rhodopsin, metarhodopsin-I, and 10-methylrhodopsin from internuclear distance measurements using 13C-labeling and 1-D rotational resonance MAS NMR.利用¹³C标记和一维旋转共振MAS NMR通过核间距离测量确定牛视紫红质、变视紫红质-I和10-甲基视紫红质中的视黄叉配体结构。
Biochemistry. 1999 Aug 31;38(35):11316-24. doi: 10.1021/bi983014e.
10
Solid-state 2H NMR relaxation illuminates functional dynamics of retinal cofactor in membrane activation of rhodopsin.固态 2H NMR 弛豫研究揭示了视黄醛膜激活中视黄醛辅因子的功能动力学。
Proc Natl Acad Sci U S A. 2011 May 17;108(20):8263-8. doi: 10.1073/pnas.1014692108. Epub 2011 Apr 28.
引用本文的文献
1
Interaction of Synthetic Cannabinoid Receptor Agonists with Cannabinoid Receptor I: Insights into Activation Molecular Mechanism.合成大麻素受体激动剂与大麻素受体 I 的相互作用：对激活分子机制的深入了解。
Int J Mol Sci. 2023 Oct 3;24(19):14874. doi: 10.3390/ijms241914874.
2
Rhodopsins: An Excitingly Versatile Protein Species for Research, Development and Creative Engineering.视紫红质：一种用于研究、开发和创新工程的极具通用性的蛋白质种类。
Front Chem. 2022 Jun 22;10:879609. doi: 10.3389/fchem.2022.879609. eCollection 2022.
3
Quantum Mechanical and Molecular Mechanics Modeling of Membrane-Embedded Rhodopsins.膜嵌入视紫红质的量子力学和分子力学建模。
J Membr Biol. 2019 Oct;252(4-5):425-449. doi: 10.1007/s00232-019-00095-0. Epub 2019 Sep 30.
4
Implications of short time scale dynamics on long time processes.短时间尺度动力学对长时间过程的影响。
Struct Dyn. 2017 Dec 22;4(6):061507. doi: 10.1063/1.4996448. eCollection 2017 Nov.
5
New views on phototransduction from atomic force microscopy and single molecule force spectroscopy on native rods.从原子力显微镜和天然视杆上的单分子力谱看光转导的新观点。
Sci Rep. 2017 Sep 20;7(1):12000. doi: 10.1038/s41598-017-11912-8.
6
Retinal orientation and interactions in rhodopsin reveal a two-stage trigger mechanism for activation.视紫红质的视网膜取向和相互作用揭示了激活的两阶段触发机制。
Nat Commun. 2016 Sep 2;7:12683. doi: 10.1038/ncomms12683.
7
Retinal Conformation Changes Rhodopsin's Dynamic Ensemble.视网膜构象变化视紫红质的动态整体。
Biophys J. 2015 Aug 4;109(3):608-17. doi: 10.1016/j.bpj.2015.06.046.
8
Structural approaches to understanding retinal proteins needed for vision.理解视觉相关视网膜蛋白的结构方法。
Curr Opin Cell Biol. 2014 Apr;27:32-43. doi: 10.1016/j.ceb.2013.11.001. Epub 2013 Nov 28.
9
Retinal ligand mobility explains internal hydration and reconciles active rhodopsin structures.视网膜配体的流动性解释了内部水合作用，并协调了活跃视蛋白的结构。
Biochemistry. 2014 Jan 21;53(2):376-85. doi: 10.1021/bi4013947. Epub 2014 Jan 8.
10
Deconstructing activation events in rhodopsin.解析视紫红质的激活事件。
J Am Chem Soc. 2013 Jul 31;135(30):10906-9. doi: 10.1021/ja4042687. Epub 2013 Jul 22.
本文引用的文献
1
6-s-cis Conformation and polar binding pocket of the retinal chromophore in the photoactivated state of rhodopsin.视紫红质光激活状态中视黄醛发色团的 6-s-cis 构象和极性结合口袋。
J Am Chem Soc. 2009 Oct 28;131(42):15160-9. doi: 10.1021/ja9034768.
2
Helix movement is coupled to displacement of the second extracellular loop in rhodopsin activation.在视紫红质激活过程中，螺旋运动与第二个细胞外环的位移相关联。
Nat Struct Mol Biol. 2009 Feb;16(2):168-75. doi: 10.1038/nsmb.1549. Epub 2009 Feb 1.
3
Location of the retinal chromophore in the activated state of rhodopsin*.视紫红质激活状态下视网膜发色团的位置*
J Biol Chem. 2009 Apr 10;284(15):10190-201. doi: 10.1074/jbc.M805725200. Epub 2009 Jan 28.
4
Crystal structure of opsin in its G-protein-interacting conformation.视蛋白处于与G蛋白相互作用构象时的晶体结构。
Nature. 2008 Sep 25;455(7212):497-502. doi: 10.1038/nature07330.
5
Agonist-induced conformational changes in bovine rhodopsin: insight into activation of G-protein-coupled receptors.激动剂诱导的牛视紫红质构象变化：深入了解G蛋白偶联受体的激活
J Mol Biol. 2008 Oct 3;382(2):539-55. doi: 10.1016/j.jmb.2008.06.084. Epub 2008 Jul 7.
6
Atomistic insights into rhodopsin activation from a dynamic model.基于动态模型对视紫红质激活的原子层面洞察。
J Am Chem Soc. 2008 Aug 6;130(31):10141-9. doi: 10.1021/ja0765520. Epub 2008 Jul 12.
7
Crystal structure of the ligand-free G-protein-coupled receptor opsin.无配体G蛋白偶联受体视蛋白的晶体结构。
Nature. 2008 Jul 10;454(7201):183-7. doi: 10.1038/nature07063. Epub 2008 Jun 18.
8
High-resolution distance mapping in rhodopsin reveals the pattern of helix movement due to activation.视紫红质中的高分辨率距离映射揭示了激活引起的螺旋运动模式。
Proc Natl Acad Sci U S A. 2008 May 27;105(21):7439-44. doi: 10.1073/pnas.0802515105. Epub 2008 May 19.
9
Changes to gonadotropin-releasing hormone (GnRH) receptor extracellular loops differentially affect GnRH analog binding and activation: evidence for distinct ligand-stabilized receptor conformations.促性腺激素释放激素（GnRH）受体细胞外环的变化对GnRH类似物的结合和激活有不同影响：不同配体稳定受体构象的证据。
Endocrinology. 2008 Jun;149(6):3118-29. doi: 10.1210/en.2008-0002. Epub 2008 Mar 20.
10
New G-protein-coupled receptor crystal structures: insights and limitations.新型G蛋白偶联受体晶体结构：见解与局限
Trends Pharmacol Sci. 2008 Feb;29(2):79-83. doi: 10.1016/j.tips.2007.11.009. Epub 2008 Jan 14.
Zotero 插件