The role of the non-covalent β-ionone-ring binding site in rhodopsin: historical and physiological perspective.
The role of the non-covalent β-ionone-ring binding site in rhodopsin: historical and physiological perspective.
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DOI：
10.1039/c5pp00158g
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Yoshizawa T
中科院分区：
文献类型：
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作者：
Matsumoto H;Iwasa T;Yoshizawa T
漂白的视紫红质通过11-顺式视黄醛和视蛋白之间的席夫碱形成而再生。人类视觉从光适应状态的恢复遵循双相动力学，并且每个适应阶段分别被分配给视锥和视杆中的两种不同类别的视色素，这表明碘视蛋白和视紫红质之间希夫碱形成的速度不同。松本和吉泽预测视紫红质中存在β-紫罗酮环结合位点，这一点已被结构研究所证实。他们假设视紫红质再生始于11-顺式-视黄醛的β-紫罗酮环部分的非共价结合，随后是席夫碱的形成。最近的生理研究表明，非共价占据β-紫罗酮环结合位点瞬时激活黑暗中的视觉转导级联。为了理解再生过程中11-顺式-视黄醛与视蛋白的非共价结合的作用，我们研究了视蛋白和11-顺式-视黄醛的视紫红质再生动力学，发现与视黄醛和游离胺之间的席夫碱形成相比，席夫碱形成加速约107倍。根据Cordes和Jencks，溶液中席夫碱的形成表现出钟形pH依赖性。然而，我们发现，视紫红质的形成是独立的pH在一个很宽的pH范围内，这表明水溶剂没有访问的席夫碱环境在其形成过程中。根据Hecht等人的研究，碘视蛋白的再生必须比视紫红质的再生快得多。这是否表明碘视蛋白中的席夫碱形成是由于其结构架构而有利的？碘视蛋白的结构一旦得到解决，就可以回答视网膜蛋白质的分子微调如何实现其暗适应功能等问题。相比之下，细菌视紫红质不需要占据明显的β-紫罗酮环结合位点，使得没有环己烯环的醛能够形成色素。研究其他视网膜蛋白的再生反应，这是很少得到的，将澄清分子结构与表型的关系和它们的生理作用。视紫红质通过非共价的11-顺式视网膜·视蛋白复合物再生，随后共价形成亚视黄基席夫碱，使得β-紫罗兰酮环结合口袋具有独特的生理作用。K2可能是视紫红质再生的限速步骤，因为缓慢的席夫碱形成。这些数字是根据Scheerer等人（2008年）和。
Bleached rhodopsin regenerates by way of the Schiff base formation between the 11-cis retinal and opsin. Recovery of human vision from light adapted states follows biphasic kinetics and each adaptive phase is assigned to two distinct classes of visual pigments in cones and rods, respectively, suggesting that the speed of Schiff base formation differs between iodopsin and rhodopsin. Matsumoto and Yoshizawa predicted the existence of a β-ionone ring-binding site in rhodopsin, which has been proven by structural studies. They postulated that rhodopsin regeneration starts with a non-covalent binding of the β-ionone ring moiety of 11-cis-retinal, followed by the Schiff base formation. Recent physiological investigation revealed that non-covalent occupation of β-ionone ring binding site transiently activates the visual transduction cascade in the dark. In order to understand the role of non-covalent binding of 11-cis-retinal to opsin during regeneration, we studied the kinetics of rhodopsin regeneration from opsin and 11-cis-retinal and found that the Schiff base formation is accelerated ~107 times compared to that between retinal and free amine. According to Cordes and Jencks, Schiff base formation in solution exhibits a bell-shaped pH dependence. However, we discovered that the rhodopsin formation is independent of pH over a wide pH range, suggesting that water solvents do not have access to the Schiff base milieu during its formation. According to Hecht et al. the regeneration of iodopsin must be significantly faster than that of rhodopsin. Does this suggest that the Schiff base formation in iodopsin is favored due to its structural architecture? Iodopsin structure once solved would answer such question as how molecular fine-tuning of retinal proteins realizes their dark adaptive functions. In contrast, bacteriorhodopsin does not require occupancy of a distinct β-ionone ring-binding site, enabling an aldehyde without the cyclohexene ring to form a pigment. Studies of regeneration reaction of other retinal proteins, which are scarcely available, would clarify the molecular structure-phenotype relationships and their physiological roles. Rhodopsin regenerates through a non-covalent 11-cis retinal·opsin complex followed by a covalent formation of retinylidene Schiff base, rendering the β-ionone ring binding pocket a distinct physiological role. k2 is likely to be the rate limiting step of rhodopsin regeneration because of slow Schiff base formation. The figures are modified from Scheerer et al. (2008) and from.