Disruption of Hydrogen-Bond Network in Rhodopsin Mutations Cause Night Blindness
Disruption of Hydrogen-Bond Network in Rhodopsin Mutations Cause Night Blindness
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DOI：
10.1016/j.jmb.2020.08.006
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发表时间：
2020-09-04
影响因子：
5.6
通讯作者：
Kandori, Hideki
中科院分区：
文献类型：
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作者：
Katayama, Kota;Takeyama, Yuri;Kandori, Hideki
视紫红质是一种光敏蛋白，与11-顺式视网膜结合作为其发色团。在黑暗中，视紫红质作为视蛋白部分和11-顺式视网膜之间的稳定复合物存在。光子的吸收将11-顺式视网膜转化为全反式视网膜，并启动我们的视觉。因此，视紫红质的暗激活率的增加降低了其光敏性，导致夜盲症。突变G90D和T941是导致夜盲症的突变，它们表现出与紫红质暗活化完全不同的物理化学特征，如11-顺式视网膜的高热异构化率和缓慢的色素再生。为了阐明G90D和T94I突变影响视紫红质暗态激活和再生的分子机制，我们对G90D和T941突变体的暗态和初级光中间态进行了光诱导差异FTIR光谱分析。FTIR光谱清楚地表明，带电v和疏水T94I突变体改变了发色团席夫碱区氢键网络，减弱了与Glu113反离子的静电相互作用。我们的研究结果进一步表明，突变型视紫质中央跨膜区域周围的水介导的氢键网络发生了改变，这让人想起了活跃的Meta-II状态。这种改变的水介导的氢键网络可能导致发色团的热异构化，并促进视紫红质暗活化。(C) 2020 Elsevier Ltd.版权所有。
Rhodopsin is the photosensitive protein, which binds to 11-cis-retinal as its chromophore. In the dark, rhodopsin exists as a stable complex between the opsin moiety and 11-cis-retinal. The absorption of a light photon converts 11-cis-retinal to all-trans-retinal and initiates our vision. As a result, the increase in the rate of dark activation of rhodopsin reduces its photosensitivity resulting in night blindness. The mutations, G90D and T941 are night blindness-causing mutations that exhibit completely different physicochemical characteristics associated with the dark activation of rhodopsin, such as a high rate of thermal isomerization of 11-cis-retinal and a slow pigment regeneration. To elucidate the molecular mechanism by which G90D and T94I mutations affect rhodopsin dark activation and regeneration, we performed light-induced difference FTIR spectroscopy on dark and primary photo-intermediate states of G90D and T941 mutants. The FTIR spectra clearly show that both charged v and hydrophobic T94I mutants alter the H-bond network at the Schiff base region of the chromophore, which weakens the electrostatic interaction with Glu113 counterion. Our results further show an altered water-mediated H-bond network around the central transmembrane region of mutant rhodopsin, which is reminiscent of the active Meta-II state. This altered water-mediated H-bond network may cause thermal isomerization of the chromophore and facilitate rhodopsin dark activation. (C) 2020 Elsevier Ltd. All rights reserved.