TY - JOUR

T1 - Small-Angle Neutron Scattering Reveals Energy Landscape for Rhodopsin Photoactivation

AU - Perera, Suchithranga M. D. C.

AU - Chawla, Udeep

AU - Shrestha, Utsab Raj

AU - Bhowmik, Debsindhu

AU - Struts, A. V.

AU - Qian, Shuo

AU - Chu, Xiang-Qiang

AU - Brown, Michael F.

N1 - Funding Information: Work was supported by the NSF (Division of Molecular and Cellular Biosciences, Grant No. 1616008 to X.-Q.C. and Grant No. 11817862 to M.F.B.) and by the NIH (Grants EY012049 and EY026041 to M.F.B.). X.-Q.C. was supported by NSAF No. U1730449. S.M.D.C.P. was supported by a Technology Research Initiative Fund (TRIF) predoctoral fellowship from the Arizona Board of Regents and by a Galileo Circle fellowship. A.V.S. was supported by the Russian Foundation for Basic Research (16-04-00494A). We thank H. Frauenfeld-er, P. Fromme, A. Garcıá, A. Grossfield, W. Heller, J. Katsaras, D. Matyushov, and V. Pingali for discussions and H. O’Neill and Q. Zhang of Oak Ridge National Laboratory (ORNL) for sample assistance. We thank C. Aspinwall for use of the dynamical light scattering instrument, K. Bao for constructing the LED light source used for the neutron scattering experiments, and A. Huang and S. Lovely for assistance with sample preparations. The High Flux Isotope Reactor, where the Bio-SANS is located, is supported by the Scientific User Facilities Division, Office of Basic Energy Sciences, U.S. Department of Energy. The Bio-SANS of the Center for Structural Molecular Biology is supported by the Office of Biological and Environmental Research of the U.S. Department of Energy. All data generated or analyzed during this study are included in the published article and its supporting materials.

PY - 2018/12/20

Y1 - 2018/12/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85058878180&partnerID=8YFLogxK

U2 - 10.1021/acs.jpclett.8b03048

DO - 10.1021/acs.jpclett.8b03048

M3 - Article

VL - 9

SP - 7064

EP - 7071

JO - Journal of Physical Chemistry Letters

JF - Journal of Physical Chemistry Letters

SN - 1948-7185

IS - 24

ER -