Structural and functional properties of metarhodopsin III: Recent spectroscopic studies on deactivation pathways of rhodopsin
Structural and functional properties of metarhodopsin III: Recent spectroscopic studies on deactivation pathways of rhodopsin
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DOI：
10.1039/b616365c
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发表时间：
2007-01-01
影响因子：
3.3
通讯作者：
Vogel, Reiner
中科院分区：
文献类型：
--
作者：
Bartl, Franz J.;Vogel, Reiner
在过去的几十年里，视紫红质的激活一直是研究人员关注的焦点，在分子水平上揭示了这种典型的G蛋白偶联受体激活途径的许多方面。该过程始于其视网膜发色团在光作用下从11 - 顺式异构化为全反式，并最终导致在向活性受体状态Meta II转变过程中大规模的螺旋运动。然而，对于光受体的失活途径知之甚少，而这些途径是维持功能性光感受器细胞的关键步骤。视紫红质的活性受体形式Meta II通过两种根本不同的途径降解，要么通过从其结合口袋释放激活的全反式视网膜配体形成脱辅基蛋白视蛋白，要么在向变视紫红质III（Meta III）转变过程中该配体热异构化为一种活性较低的形式。这两种降解产物，视蛋白和Meta III，在生理条件下基本无活性，但它们并不能恢复暗态的完全无活性。尽管Meta III的一些特性在20世纪60年代就已被描述，但它的分子性质及其形成途径仍然相当模糊。在这篇综述中，我们重点关注我们实验室的近期研究，这些研究在我们对视紫红质Meta III失活途径及其潜在生理作用的理解上取得了重大进展。我们利用傅里叶变换红外（FTIR）差谱技术，并结合多种其他光谱学、生物化学技术以及量子化学计算，对视网膜配体和受体蛋白之间的相互作用有了一个总体认识，并将其与无脊椎动物光感受器和微生物视网膜蛋白中的类似反应机制进行了比较。
The activation of rhodopsin has been the focus of researchers over the past decades, revealing many aspects of the activation pathways of this prototypical G protein-coupled receptor on a molecular level, starting with the light-dependent isomerization of its retinal chromophore from 11-cis to all-trans and leading eventually to the large scale helix movements in the transition to the active receptor state, Meta II. Comparatively little is known, however, on the deactivation pathways of the light receptor, which represent essential steps in maintaining a functional photoreceptor cell. Rhodopsin's active receptor species, Meta II, decays by two fundamentally different pathways, either forming the apoprotein opsin by release of the activating all-trans retinal ligand from its binding pocket, or by a thermal isomerization of this ligand to a less activating species in the transition to metarhodopsin III (Meta III). Both decay products, opsin and Meta III, are largely inactive under physiological conditions, yet they do not restore the complete inactivity of the dark state. Although some properties of Meta III have been described already in the 1960s, its molecular nature and the pathways of its formation have remained rather obscure. In this review, we focus on recent studies from our laboratories, which have provided a major progress in our understanding of the Meta III deactivation pathway and its potential physiological roles. Using Fourier-transform infrared (FTIR) difference spectroscopy in combination with a variety of other spectroscopic and biochemical techniques and quantum chemical calculations, we have developed a general picture of the interplay between the retinal ligand and the receptor protein, which is compared to similar reaction mechanisms in invertebrate photoreceptors and microbial retinal proteins.