Coupling of retinal isomerization to the activation of rhodopsin
Coupling of retinal isomerization to the activation of rhodopsin
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DOI：
10.1073/pnas.0402848101
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发表时间：
2004-07-06
影响因子：
11.1
通讯作者：
Smith, SO
中科院分区：
文献类型：
--
作者：
Patel, AB;Crocker, E;Smith, SO
视色素视紫红质的激活是由其视网膜发色团的11-顺式到-反式异构化引起的。对视紫红质和变视紫红质II中间体的高分辨率固态NMR测量显示了视网膜异构化如何破坏在黑暗中锁定受体的螺旋相互作用。我们做了2D偶极辅助旋转共振核磁共振测量之间的C-13-标签的视网膜发色团和特定的C-13-标签的酪氨酸，甘氨酸，丝氨酸和苏氨酸的视网膜结合位点的视紫红质。异构化轨迹的基本方面是C20甲基朝向细胞外环2的大旋转和视网膜发色团朝向跨膜螺旋5的4至5埃平移。在活性后视紫红质II中间体中观察到的视网膜-蛋白质接触表明A类G蛋白偶联受体涉及跨膜螺旋5、6和7的偶联运动的一般活化机制。
Activation of the visual pigment rhodopsin is caused by 11-cis to -trans isomerization of its retinal chromophore. High-resolution solid-state NMR measurements on both rhodopsin and the metarhodopsin II intermediate show how retinal isomerization disrupts helix interactions that lock the receptor off in the dark. We made 2D dipolar-assisted rotational resonance NMR measurements between C-13-labels on the retinal chromophore and specific C-13-labels on tyrosine, glycine, serine, and threonine in the retinal binding site of rhodopsin. The essential aspects of the isomerization trajectory are a large rotation of the C20 methyl group toward extracellular loop 2 and a 4- to 5-Angstrom translation of the retinal chromophore toward transmembrane helix 5. The retinal-protein contacts observed in the active metarhodopsin II intermediate suggest a general activation mechanism for class A G protein-coupled receptors involving coupled motion of transmembrane helices 5, 6, and 7.