Light Activation of Rhodopsin: Insights from Molecular Dynamics Simulations Guided by Solid-State NMR Distance Restraints

被引：46

作者：

Hornak, Viktor ^{[1
]}

Ahuja, Shivani ^{[2
]}

Eilers, Markus ^{[1
]}

Goncalves, Joseph A. ^{[1
]}

Sheves, Mordechai ^{[3
]}

Reeves, Philip J. ^{[4
]}

Smith, Steven O. ^{[1
]}

机构：

[1] SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA

[2] SUNY Stony Brook, Dept Phys & Astron, Stony Brook, NY 11794 USA

[3] Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel

[4] Univ Essex, Dept Biol Sci, Colchester C04 3SQ, Essex, England

来源：

JOURNAL OF MOLECULAR BIOLOGY | 2010年 / 396卷 / 03期

基金：

美国国家卫生研究院;

关键词：

rhodopsin; G-protein-coupled receptors; NMR; molecular dynamics; retinal; PROTEIN-COUPLED RECEPTOR; 2ND EXTRACELLULAR LOOP; PROTONATED SCHIFF-BASE; INFRARED DIFFERENCE SPECTROSCOPY; VISUAL PIGMENT ANALOG; HIGH-LEVEL EXPRESSION; MAMMALIAN-CELL LINES; TOGGLE SWITCH MODEL; RETINAL CHROMOPHORE; CRYSTAL-STRUCTURE;

D O I：

10.1016/j.jmb.2009.12.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Structural restraints provided by solid-state NMR measurements of the metarhodopsin 11 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 H intermediate (>1 ms) is beyond that readily accessible by molecular dynamics, we use NMR distance restraints derived from C-13 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. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：510 / 527

页数：18

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