Small-Angle Neutron Scattering Reveals Energy Landscape for Rhodopsin Photoactivation

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 c...

Full description

Saved in:
Bibliographic Details
Published in:The journal of physical chemistry letters 2018-12, Vol.9 (24), p.7064-7071
Main Authors: Perera, Suchithranga M. D. C, Chawla, Udeep, Shrestha, Utsab R, Bhowmik, Debsindhu, Struts, Andrey V, Qian, Shuo, Chu, Xiang-Qiang, Brown, Michael F
Format: Article
Language:English
Subjects:
detergent
energy landscape
GPCR
hydration
INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
membrane proteins
neutron scattering
protein dynamics
Rhodopsin
slaving
vision
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1948-7185
1948-7185
DOI:10.1021/acs.jpclett.8b03048