小柯机器人

瑞士Paul Scherrer研究所Valerie Panneels等研究人员合作发现，超快的结构变化引导视觉的第一个分子事件。相关论文于2023年3月22日在线发表在《自然》杂志上。

研究人员利用室温下的超快时间分辨晶体学来确定了异构化的扭曲全反式视紫红质如何储存光子能量，而这种能量是启动与形成G蛋白结合信号状态有关的蛋白质构象变化所必需的。在光激活后1皮秒的时间延迟中，扭曲的视网膜已经从其与结合口袋的众多相互作用中抽离出一半，多余的光子能量通过一个各向异性的蛋白质呼吸运动在细胞外空间方向释放。值得注意的是，视紫红质蛋白质侧链的早期结构运动出现在参与保守的A类G蛋白偶联受体（GPCR）激活机制的后期阶段的区域。这项研究揭示了脊椎动物视觉的最早阶段，并指出了激动剂介导GPCR激活的分子机制。

据介绍，视觉是由对光敏感的GPCR的视紫红质家族启动的。一个光子被视紫红质的11顺式视网膜发色团吸收，它在200飞秒内异构为全反式构象，从而启动了最终导致视觉的细胞信号转导过程。然而，光活化的视网膜诱导视紫红质内部激活事件的分子内机制在实验上仍不清楚。

附：英文原文

Title: Ultrafast structural changes direct the first molecular events of vision

Author: Gruhl, Thomas, Weinert, Tobias, Rodrigues, Matthew J., Milne, Christopher J., Ortolani, Giorgia, Nass, Karol, Nango, Eriko, Sen, Saumik, Johnson, Philip J. M., Cirelli, Claudio, Furrer, Antonia, Mous, Sandra, Skopintsev, Petr, James, Daniel, Dworkowski, Florian, Bth, Petra, Kekilli, Demet, Ozerov, Dmitry, Tanaka, Rie, Glover, Hannah, Bacellar, Camila, Brnle, Steffen, Casadei, Cecilia M., Diethelm, Azeglio D., Gashi, Dardan, Gotthard, Guillaume, Guix-Gonzlez, Ramon, Joti, Yasumasa, Kabanova, Victoria, Knopp, Gregor, Lesca, Elena, Ma, Pikyee, Martiel, Isabelle, Mhle, Jonas, Owada, Shigeki, Pamula, Filip, Sarabi, Daniel, Tejero, Oliver, Tsai, Ching-Ju, Varma, Niranjan, Wach, Anna, Boutet, Sbastien, Tono, Kensuke, Nogly, Przemyslaw, Deupi, Xavier, Iwata, So, Neutze, Richard, Standfuss, Jrg, Schertler, Gebhard, Panneels, Valerie

Issue&Volume: 2023-03-22

Abstract: Vision is initiated by the rhodopsin family of light-sensitive G protein-coupled receptors (GPCRs)1. A photon is absorbed by the 11-cis retinal chromophore of rhodopsin, which isomerizes within 200femtoseconds to the all-trans conformation2, thereby initiating the cellular signal transduction processes that ultimately lead to vision. However, the intramolecular mechanism by which the photoactivated retinal induces the activation events inside rhodopsin remains experimentally unclear. Here we use ultrafast time-resolved crystallography at room temperature3 to determine how an isomerized twisted all-trans retinal stores the photon energy that is required to initiate the protein conformational changes associated with the formation of the G protein-binding signalling state. The distorted retinal at a 1-ps time delay after photoactivation has pulled away from half of its numerous interactions with its binding pocket, and the excess of the photon energy is released through an anisotropic protein breathing motion in the direction of the extracellular space. Notably, the very early structural motions in the protein side chains of rhodopsin appear in regions that are involved in later stages of the conserved class A GPCR activation mechanism. Our study sheds light on the earliest stages of vision in vertebrates and points to fundamental aspects of the molecular mechanisms of agonist-mediated GPCR activation.

DOI: 10.1038/s41586-023-05863-6

Source: https://www.nature.com/articles/s41586-023-05863-6

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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