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视紫红质的光激活：固态 NMR 距离约束指导下的分子动力学模拟的新见解。

Light activation of rhodopsin: insights from molecular dynamics simulations guided by solid-state NMR distance restraints.

机构信息

Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, USA.

出版信息

J Mol Biol. 2010 Feb 26;396(3):510-27. doi: 10.1016/j.jmb.2009.12.003. Epub 2009 Dec 11.

DOI:10.1016/j.jmb.2009.12.003
PMID:20004206
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2822010/
Abstract

Structural restraints provided by solid-state NMR measurements of the metarhodopsin II intermediate are combined with molecular dynamics simulations to help visualize structural changes in the light activation of rhodopsin. Since the timescale for the formation of the metarhodopsin II intermediate (>1 ms) is beyond that readily accessible by molecular dynamics, we use NMR distance restraints derived from 13C dipolar recoupling measurements to guide the simulations. The simulations yield a working model for how photoisomerization of the 11-cis retinylidene chromophore bound within the interior of rhodopsin is coupled to transmembrane helix motion and receptor activation. The mechanism of activation that emerges is that multiple switches on the extracellular (or intradiscal) side of rhodopsin trigger structural changes that converge to disrupt the ionic lock between helices H3 and H6 on the intracellular side of the receptor.

摘要

固态 NMR 测量对视紫红质 II 中间态的结构限制与分子动力学模拟相结合，有助于可视化视紫红质光激活过程中的结构变化。由于形成视紫红质 II 中间态的时间尺度（>1 ms）超出了分子动力学的可及范围，我们使用来自 13C 偶极重聚测量的 NMR 距离限制来指导模拟。模拟产生了一个工作模型，说明结合在视紫红质内部的 11-顺式视黄醛发色团的光异构化如何与跨膜螺旋运动和受体激活偶联。出现的激活机制是，视紫红质细胞外（或盘内）侧的多个开关触发结构变化，这些变化汇聚在一起破坏受体细胞内侧的 H3 和 H6 螺旋之间的离子锁。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6988/2822010/b32a155195fe/nihms-164776-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6988/2822010/633ed7f84db9/nihms-164776-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6988/2822010/15654a3f2113/nihms-164776-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6988/2822010/632e4ed379ea/nihms-164776-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6988/2822010/eab2858062cd/nihms-164776-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6988/2822010/95e0256d8f99/nihms-164776-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6988/2822010/9f6728b4d285/nihms-164776-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6988/2822010/aad4e87d59bf/nihms-164776-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6988/2822010/130abcaff426/nihms-164776-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6988/2822010/b32a155195fe/nihms-164776-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6988/2822010/633ed7f84db9/nihms-164776-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6988/2822010/15654a3f2113/nihms-164776-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6988/2822010/632e4ed379ea/nihms-164776-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6988/2822010/eab2858062cd/nihms-164776-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6988/2822010/95e0256d8f99/nihms-164776-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6988/2822010/9f6728b4d285/nihms-164776-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6988/2822010/aad4e87d59bf/nihms-164776-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6988/2822010/130abcaff426/nihms-164776-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6988/2822010/b32a155195fe/nihms-164776-f0009.jpg

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