Uncovering the triggers for GPCR activation using solid-state NMR spectroscopy.
J Magn Reson. 2015 Apr;253:111-8
Authors: Kimata N, Reeves PJ, Smith SO
Abstract
G protein-coupled receptors (GPCRs) span cell membranes with seven transmembrane helices and respond to a diverse array of extracellular signals. Crystal structures of GPCRs have provided key insights into the architecture of these receptors and the role of conserved residues. However, the question of how ligand binding induces the conformational changes that are essential for activation remains largely unanswered. Since the extracellular sequences and structures of GPCRs are not conserved between receptor subfamilies, it is likely that the initial molecular triggers for activation vary depending on the specific type of ligand and receptor. In this article, we describe NMR studies on the rhodopsin subfamily of GPCRs and propose a mechanism for how retinal isomerization switches the receptor to the active conformation. These results suggest a general approach for determining the triggers for activation in other GPCR subfamilies using NMR spectroscopy.
[NMR paper] Uncovering the triggers for GPCR activation using solid-state NMR spectroscopy
Uncovering the triggers for GPCR activation using solid-state NMR spectroscopy
Publication date: April 2015
Source:Journal of Magnetic Resonance, Volume 253</br>
Author(s): Naoki Kimata , Philip J. Reeves , Steven O. Smith</br>
G protein-coupled receptors (GPCRs) span cell membranes with seven transmembrane helices and respond to a diverse array of extracellular signals. Crystal structures of GPCRs have provided key insights into the architecture of these receptors and the role of conserved residues. However, the question of how ligand binding induces the...
[NMR paper] G-protein-coupled receptor structure, ligand binding and activation as studied by solid-state NMR spectroscopy.
G-protein-coupled receptor structure, ligand binding and activation as studied by solid-state NMR spectroscopy.
G-protein-coupled receptor structure, ligand binding and activation as studied by solid-state NMR spectroscopy.
Biochem J. 2013 Mar 15;450(3):443-57
Authors: Ding X, Zhao X, Watts A
Abstract
GPCRs (G-protein-coupled receptors) are versatile signalling molecules at the cell surface and make up the largest and most diverse family of membrane receptors in the human genome. They convert a large variety of extracellular stimuli into...
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03-01-2013 09:57 PM
[NMR paper] Conformational Ensembles in GPCR Activation.
Conformational Ensembles in GPCR Activation.
Related Articles Conformational Ensembles in GPCR Activation.
Cell. 2013 Jan 31;152(3):385-6
Authors: Vardy E, Roth BL
Abstract
Recent advances in G-protein-coupled receptor structural biology have provided only limited insight into the active conformations of these key signaling molecules. A paper from Nygaard et*al. reveals the dynamic nature of GPCRs along the activation pathway by complementing NMR experiments with ultralong-timescale molecular dynamics simulations.
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Molecular simulations and solid-state NMR investigate dynamical structure in rhodopsin activation.
Molecular simulations and solid-state NMR investigate dynamical structure in rhodopsin activation.
Molecular simulations and solid-state NMR investigate dynamical structure in rhodopsin activation.
Biochim Biophys Acta. 2011 Aug 8;
Authors: Mertz B, Struts AV, Feller SE, Brown MF
Abstract
Rhodopsin has served as the primary model for studying G protein-coupled receptors (GPCRs)-the largest group in the human genome, and consequently a primary target for pharmaceutical development. Understanding the functions and activation mechanisms of...
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08-20-2011 03:31 PM
Solid-state 2H NMR relaxation illuminates functional dynamics of retinal cofactor in membrane activation of rhodopsin [Biophysics and Computational Biology]
Solid-state 2H NMR relaxation illuminates functional dynamics of retinal cofactor in membrane activation of rhodopsin
Struts, A. V., Salgado, G. F. J., Brown, M. F....
Date: 2011-05-17
Rhodopsin is a canonical member of the family of G protein-coupled receptors, which transmit signals across cellular membranes and are linked to many drug interventions in humans. Here we show that solid-state 2H NMR relaxation allows investigation of light-induced changes in local ps–ns time scale motions of retinal bound to rhodopsin. Site-specific 2H labels were introduced into methyl groups of the...
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Solid-state 2H NMR relaxation illuminates functional dynamics of retinal cofactor in membrane activation of rhodopsin.
Solid-state 2H NMR relaxation illuminates functional dynamics of retinal cofactor in membrane activation of rhodopsin.
Solid-state 2H NMR relaxation illuminates functional dynamics of retinal cofactor in membrane activation of rhodopsin.
Proc Natl Acad Sci U S A. 2011 Apr 28;
Authors: Struts AV, Salgado GF, Brown MF
Rhodopsin is a canonical member of the family of G protein-coupled receptors, which transmit signals across cellular membranes and are linked to many drug interventions in humans. Here we show that solid-state (2)H NMR relaxation...
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04-30-2011 12:36 PM
Solid-state NMR and SAXS studies provide a structural basis for the activation of alp
Solid-state NMR and SAXS studies provide a structural basis for the activation of alphaB-crystallin oligomers.
Related Articles Solid-state NMR and SAXS studies provide a structural basis for the activation of alphaB-crystallin oligomers.
Nat Struct Mol Biol. 2010 Aug 29;
Authors: Jehle S, Rajagopal P, Bardiaux B, Markovic S, Kühne R, Stout JR, Higman VA, Klevit RE, van Rossum BJ, Oschkinat H
The small heat shock protein alphaB-crystallin (alphaB) contributes to cellular protection against stress. For decades, high-resolution structural studies on...
Uncovering the triggers for GPCR activation using solid-state NMR spectroscopy.
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