Location of Trp265 in metarhodopsin II: Implications for the activation mechanism of the visual receptor rhodopsin
Location of Trp265 in metarhodopsin II: Implications for the activation mechanism of the visual receptor rhodopsin
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DOI：
10.1016/j.jmb.2005.12.046
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发表时间：
2006-03-17
影响因子：
5.6
通讯作者：
Smith, SO
中科院分区：
文献类型：
--
作者：
Crocker, E;Eilers, M;Smith, SO
视紫红质中II-顺式视网膜生色团的异构化与跨膜螺旋H6的运动和受体的激活相耦合。我们给出了视紫红质和变视紫质II中间体的固态魔角旋转核磁共振测量，支持Trp265(6.48)与视网膜发色团的相互作用负责在黑暗中稳定不活跃的构象，并且β-紫罗兰酮环的运动允许Trp2656.48和跨膜螺旋H6在光中采用活跃的构象。在视网膜的C19和C20-甲基以及均匀标记的C-13标记的Trp265(6.48)之间进行了二维偶极辅助旋转共振核磁共振测量。在视紫红质的暗态下，视网膜中存在的C20-Trp265(6.48)接触在视紫红质II中丢失，并与C19甲基形成新的接触。我们以前已经证明，在视紫红质II中，视网膜向H5平移4-5埃。这一运动与Trp-C19接触一起，意味着Trp265(6.48)侧链在视紫红质激活时显著移动。核磁共振测量还表明，视紫红质中Trp265(6.48)和Gly121(3.36)之间的堆积作用在变视紫红质II中消失，与H6离开H3的运动一致。然而，在视紫红质和变视紫质II中都观察到H3上的Gly120(3.35)和H2上的Met86(2.53)之间的密切接触，这表明H3在受体激活时不会显著改变取向。(C)2005爱思唯尔有限公司。保留所有权利。
Isomerization of the II-cis retinal chromophore in the visual pigment rhodopsin is coupled to motion of transmembrane helix H6 and receptor activation. We present solid-state magic angle spinning NMR measurements of rhodopsin and the metarhodopsin II intermediate that support the proposal that interaction of Trp265(6.48) with the retinal chromophore is responsible for stabilizing an inactive conformation in the dark, and that motion of the beta-ionone ring allows Trp2656.48 and transmembrane helix H6 to adopt active conformations in the light. Two-dimensional dipolar-assisted rotational resonance NMR measurements are made between the C19 and C20-methyl groups of the retinal and uniformly C-13-labeled Trp265(6.48). The retinal C20-Trp265(6.48) contact present in the dark-state of rhodopsin is lost in metarhodopsin II, and a new contact is formed with the C19 methyl group. We have previously shown that the retinal translates 4-5 angstrom toward H5 in metarhodopsin II. This motion, in conjunction with the Trp-C19 contact, implies that the Trp265(6.48) side-chain moves significantly upon rhodopsin activation. NMR measurements also show that a packing interaction in rhodopsin between Trp265(6.48) and Gly121(3.36) is lost in metarhodopsin II, consistent with H6 motion away from H3. However, a close contact between Gly120(3.35) on H3 and Met86(2.53) on H2 is observed in both rhodopsin and metarhodopsin II, suggesting that H3 does not change orientation significantly upon receptor activation. (c) 2005 Elsevier Ltd. All rights reserved.