The Library
Vibrational resonance, allostery, and activation in rhodopsin-like G protein-coupled receptors
Tools
Woods, Kristina N., Pfeffer, Jürgen, Dutta, Arpana and Klein-Seetharaman, Judith (2016) Vibrational resonance, allostery, and activation in rhodopsin-like G protein-coupled receptors. Scientific Reports, 6 . 37290. doi:10.1038/srep37290 ISSN 2045-2322.
PDF
WRAP_9577424-wms_deans_office-300117-srep37290.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (2479Kb) |
Official URL: http://dx.doi.org/10.1038/srep37290
Abstract
G protein-coupled receptors are a large family of membrane proteins activated by a variety of structurally diverse ligands making them highly adaptable signaling molecules. Despite recent advances in the structural biology of this protein family, the mechanism by which ligands induce allosteric changes in protein structure and dynamics for its signaling function remains a mystery. Here, we propose the use of terahertz spectroscopy combined with molecular dynamics simulation and protein evolutionary network modeling to address the mechanism of activation by directly probing the concerted fluctuations of retinal ligand and transmembrane helices in rhodopsin. This approach allows us to examine the role of conformational heterogeneity in the selection and stabilization of specific signaling pathways in the photo-activation of the receptor. We demonstrate that ligand-induced shifts in the conformational equilibrium prompt vibrational resonances in the protein structure that link the dynamics of conserved interactions with fluctuations of the active-state ligand. The connection of vibrational modes creates an allosteric association of coupled fluctuations that forms a coherent signaling pathway from the receptor ligand-binding pocket to the G-protein activation region. Our evolutionary analysis of rhodopsin-like GPCRs suggest that specific allosteric sites play a pivotal role in activating structural fluctuations that allosterically modulate functional signals.
Item Type: | Journal Article | ||||||||
---|---|---|---|---|---|---|---|---|---|
Subjects: | Q Science > QP Physiology | ||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
||||||||
Library of Congress Subject Headings (LCSH): | G proteins, Membrane proteins, Ligands, Rhodopsin | ||||||||
Journal or Publication Title: | Scientific Reports | ||||||||
Publisher: | Nature Publishing Group | ||||||||
ISSN: | 2045-2322 | ||||||||
Official Date: | 16 November 2016 | ||||||||
Dates: |
|
||||||||
Volume: | 6 | ||||||||
Article Number: | 37290 | ||||||||
DOI: | 10.1038/srep37290 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||
Date of first compliant deposit: | 31 January 2017 | ||||||||
Date of first compliant Open Access: | 2 February 2017 |
Request changes or add full text files to a record
Repository staff actions (login required)
View Item |
Downloads
Downloads per month over past year