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Title: Small-Angle Neutron Scattering Reveals Energy Landscape for Rhodopsin Photoactivation

Abstract

Here, knowledge of the activation principles for G-protein-coupled receptors (GPCRs) is critical to development of new pharmaceuticals. Rhodopsin is the archetype for the largest GPCR family, yet the changes in protein dynamics that trigger signaling are not fully understood. Here we show that rhodopsin can be investigated by small-angle neutron scattering (SANS) in fully protiated detergent micelles under contrast matching to resolve light-induced changes in the protein structure. In SANS studies of membrane proteins, the zwitterionic detergent [(cholamidopropyl)dimethylammonio]-propanesulfonate (CHAPS) is advantageous because of the low contrast difference between the hydrophobic core and hydrophilic head groups as compared with alkyl glycoside detergents. Combining SANS results with quasielastic neutron scattering reveals how changes in volumetric protein shape are coupled (slaved) to the aqueous solvent. Upon light exposure, rhodopsin is swollen by the penetration of water into the protein core, allowing interactions with effector proteins in the visual signaling mechanism.

Authors:
 [1];  [2];  [3]; ORCiD logo [3];  [4]; ORCiD logo [5]; ORCiD logo [6]; ORCiD logo [1]
  1. Univ. of Arizona, Tucson, AZ (United States)
  2. Univ. of Arizona, Tucson, AZ (United States); Univ. of Kentucky, Lexington, KY (United States)
  3. Wayne State Univ., Detroit, MI (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  4. Univ. of Arizona, Tucson, AZ (United States); St. Petersburg State Univ., St. Petersburg (Russia)
  5. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  6. Graduate School of China Academy of Engineering Physics, Beijing (China)
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1492157
Grant/Contract Number:  
AC05-00OR22725
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Journal of Physical Chemistry Letters
Additional Journal Information:
Journal Volume: 9; Journal Issue: 24; Journal ID: ISSN 1948-7185
Publisher:
American Chemical Society
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; detergent; energy landscape; GPCR; hydration; membrane proteins; neutron scattering; protein dynamics; Rhodopsin; slaving; vision

Citation Formats

Perera, Suchithranga M. D. C., Chawla, Udeep, Shrestha, Utsab R., Bhowmik, Debsindhu, Struts, Andrey V., Qian, Shuo, Chu, Xiang -Qiang, and Brown, Michael F. Small-Angle Neutron Scattering Reveals Energy Landscape for Rhodopsin Photoactivation. United States: N. p., 2018. Web. doi:10.1021/acs.jpclett.8b03048.
Perera, Suchithranga M. D. C., Chawla, Udeep, Shrestha, Utsab R., Bhowmik, Debsindhu, Struts, Andrey V., Qian, Shuo, Chu, Xiang -Qiang, & Brown, Michael F. Small-Angle Neutron Scattering Reveals Energy Landscape for Rhodopsin Photoactivation. United States. https://doi.org/10.1021/acs.jpclett.8b03048
Perera, Suchithranga M. D. C., Chawla, Udeep, Shrestha, Utsab R., Bhowmik, Debsindhu, Struts, Andrey V., Qian, Shuo, Chu, Xiang -Qiang, and Brown, Michael F. 2018. "Small-Angle Neutron Scattering Reveals Energy Landscape for Rhodopsin Photoactivation". United States. https://doi.org/10.1021/acs.jpclett.8b03048. https://www.osti.gov/servlets/purl/1492157.
@article{osti_1492157,
title = {Small-Angle Neutron Scattering Reveals Energy Landscape for Rhodopsin Photoactivation},
author = {Perera, Suchithranga M. D. C. and Chawla, Udeep and Shrestha, Utsab R. and Bhowmik, Debsindhu and Struts, Andrey V. and Qian, Shuo and Chu, Xiang -Qiang and Brown, Michael F.},
abstractNote = {Here, knowledge of the activation principles for G-protein-coupled receptors (GPCRs) is critical to development of new pharmaceuticals. Rhodopsin is the archetype for the largest GPCR family, yet the changes in protein dynamics that trigger signaling are not fully understood. Here we show that rhodopsin can be investigated by small-angle neutron scattering (SANS) in fully protiated detergent micelles under contrast matching to resolve light-induced changes in the protein structure. In SANS studies of membrane proteins, the zwitterionic detergent [(cholamidopropyl)dimethylammonio]-propanesulfonate (CHAPS) is advantageous because of the low contrast difference between the hydrophobic core and hydrophilic head groups as compared with alkyl glycoside detergents. Combining SANS results with quasielastic neutron scattering reveals how changes in volumetric protein shape are coupled (slaved) to the aqueous solvent. Upon light exposure, rhodopsin is swollen by the penetration of water into the protein core, allowing interactions with effector proteins in the visual signaling mechanism.},
doi = {10.1021/acs.jpclett.8b03048},
url = {https://www.osti.gov/biblio/1492157}, journal = {Journal of Physical Chemistry Letters},
issn = {1948-7185},
number = 24,
volume = 9,
place = {United States},
year = {Thu Nov 29 00:00:00 EST 2018},
month = {Thu Nov 29 00:00:00 EST 2018}
}

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Cited by: 13 works
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Works referencing / citing this record:

Neutron scattering in the biological sciences: progress and prospects
journal, December 2018


Quantum Mechanical and Molecular Mechanics Modeling of Membrane-Embedded Rhodopsins
journal, September 2019