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

Shrestha, Utsab R.; Perera, Suchithranga M. D. C.; Bhowmik, Debsindhu; Chawla, Udeep; Mamontov, Eugene; Brown, Michael F.; Chu, Xiang -Qiang

doi:10.1021/acs.jpclett.6b01632

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

Journal Article · Thu Sep 15 00:00:00 EDT 2016 · Journal of Physical Chemistry Letters

DOI:https://doi.org/10.1021/acs.jpclett.6b01632· OSTI ID:1329160

Shrestha, Utsab R. ^[1]; Perera, Suchithranga M. D. C. ^[2]; Bhowmik, Debsindhu ^[3]; Chawla, Udeep ^[2]; Mamontov, Eugene ^[4]; Brown, Michael F. ^[2]; Chu, Xiang -Qiang ^[1]

Wayne State Univ., Detroit, MI (United States)
Univ. of Arizona, Tucson, AZ (United States)
Wayne State Univ., Detroit, MI (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

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.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States). Spallation Neutron Source

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 1329160

Journal Information:: Journal of Physical Chemistry Letters, Journal Name: Journal of Physical Chemistry Letters Vol. 7; ISSN 1948-7185

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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