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. Furthermore, 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.
| Original language | English |
|---|---|
| Pages (from-to) | 4130-4136 |
| Number of pages | 7 |
| Journal | Journal of Physical Chemistry Letters |
| Volume | 7 |
| Issue number | 20 |
| DOIs | |
| State | Published - Oct 20 2016 |
Funding
This work was funded and supported by Wayne State University. The neutron scattering experiment at the Oak Ridge National Laboratory (ORNL) Spallation Neutron Source was sponsored by the Scientific User Facilities Division, Office of Basic Energy Sciences, U.S. Department of Energy. ORNL is managed by UT Battelle, LLC, for the U.S. Department of Energy (DOE) under Contract No. DE-AC05-00OR22725. This work is partially supported by the National Science Foundation, Division of Molecular and Cellular Biosciences (DMCB), under Grant No. 1616008. We thank Drs. H. M. O Neill and Q. Zhang of Oak Ridge National Laboratory for their help during the preparation of the sample environment.