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Title: Quasi-elastic neutron scattering reveals ligand-induced protein dynamics of a G-protein-coupled receptor

Abstract

Light activation of the visual G-protein-coupled receptor (GPCR) rhodopsin leads to significant structural fluctuations of the protein embedded within the membrane yielding the activation of cognate G-protein (transducin), which initiates biological signaling. Here, we report a quasi-elastic neutron scattering study of the activation of rhodopsin as a GPCR prototype. Our results reveal a broadly distributed relaxation of hydrogen atom dynamics of rhodopsin on a picosecond–nanosecond time scale, crucial for protein function, as only observed for globular proteins previously. Interestingly, the results suggest significant differences in the intrinsic protein dynamics of the dark-state rhodopsin versus the ligand-free apoprotein, opsin. These differences can be attributed to the influence of the covalently bound retinal ligand. Moreover, an idea of the generic free-energy landscape is used to explain the GPCR dynamics of ligand-binding and ligand-free protein conformations, which can be further applied to other GPCR systems.

Authors:
 [1];  [2];  [3];  [2];  [4];  [2];  [1]
+ Show Author Affiliations
  1. Wayne State Univ., Detroit, MI (United States)
  2. Univ. of Arizona, Tucson, AZ (United States)
  3. Wayne State Univ., Detroit, MI (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  4. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Spallation Neutron Source (SNS)
Sponsoring Org.:
USDOE
OSTI Identifier:
1329160
Grant/Contract Number:  
AC05-00OR22725
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Physical Chemistry Letters
Additional Journal Information:
Journal Volume: 7; Journal ID: ISSN 1948-7185
Publisher:
American Chemical Society
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Shrestha, Utsab R., Perera, Suchithranga M. D. C., Bhowmik, Debsindhu, Chawla, Udeep, Mamontov, Eugene, Brown, Michael F., and Chu, Xiang -Qiang. Quasi-elastic neutron scattering reveals ligand-induced protein dynamics of a G-protein-coupled receptor. United States: N. p., 2016. Web. doi:10.1021/acs.jpclett.6b01632.
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Shrestha, Utsab R., Perera, Suchithranga M. D. C., Bhowmik, Debsindhu, Chawla, Udeep, Mamontov, Eugene, Brown, Michael F., & Chu, Xiang -Qiang. Quasi-elastic neutron scattering reveals ligand-induced protein dynamics of a G-protein-coupled receptor. United States. https://doi.org/10.1021/acs.jpclett.6b01632
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Shrestha, Utsab R., Perera, Suchithranga M. D. C., Bhowmik, Debsindhu, Chawla, Udeep, Mamontov, Eugene, Brown, Michael F., and Chu, Xiang -Qiang. Thu . "Quasi-elastic neutron scattering reveals ligand-induced protein dynamics of a G-protein-coupled receptor". United States. https://doi.org/10.1021/acs.jpclett.6b01632. https://www.osti.gov/servlets/purl/1329160.
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@article{osti_1329160,
title = {Quasi-elastic neutron scattering reveals ligand-induced protein dynamics of a G-protein-coupled receptor},
author = {Shrestha, Utsab R. and Perera, Suchithranga M. D. C. and Bhowmik, Debsindhu and Chawla, Udeep and Mamontov, Eugene and Brown, Michael F. and Chu, Xiang -Qiang},
abstractNote = {Light activation of the visual G-protein-coupled receptor (GPCR) rhodopsin leads to significant structural fluctuations of the protein embedded within the membrane yielding the activation of cognate G-protein (transducin), which initiates biological signaling. Here, we report a quasi-elastic neutron scattering study of the activation of rhodopsin as a GPCR prototype. Our results reveal a broadly distributed relaxation of hydrogen atom dynamics of rhodopsin on a picosecond–nanosecond time scale, crucial for protein function, as only observed for globular proteins previously. Interestingly, the results suggest significant differences in the intrinsic protein dynamics of the dark-state rhodopsin versus the ligand-free apoprotein, opsin. These differences can be attributed to the influence of the covalently bound retinal ligand. Moreover, an idea of the generic free-energy landscape is used to explain the GPCR dynamics of ligand-binding and ligand-free protein conformations, which can be further applied to other GPCR systems.},
doi = {10.1021/acs.jpclett.6b01632},
journal = {Journal of Physical Chemistry Letters},
number = ,
volume = 7,
place = {United States},
year = {Thu Sep 15 00:00:00 EDT 2016},
month = {Thu Sep 15 00:00:00 EDT 2016}
}
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https://doi.org/10.1021/acs.jpclett.6b01632
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    Works referencing / citing this record:

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