Unraveling the Molecular Dynamics of G-Protein–Coupled Receptors

Spring 2017
Speaker: 
Michael Brown
Affiliation: 
University of Arizona
Wed, 2017-03-22
3:00PM
487 GWC
Host: 
Oliver Beckstein

Rhodopsin is the prototype for the Family A G-protein–coupled receptors (GPCRs), which are the targets of the majority of human pharmaceuticals. When we started this work, the only X-ray structure for a GPCR was rhodopsin in the dark state.  Our group has been combining experimental solid-state NMR data with molecular dynamics (MD) simulations and scattering methods to investigate visual signaling. All-atom MD simulations are conducted to model rhodopsin activation, and its interactions with signaling proteins like transducin.  We were first to discover a surprising influx of bulk water into the protein core, yielding activation of rhodopsin. Biophysical properties of the lipid bilayer affect rhodopsin activation by coupling the protein shape to the curvature stress field of the membrane.  Our solid-state NMR studies together with X-ray and neutron scattering studies reveal how light excitation energy underlies a dynamical receptor mechanism in a membrane lipid environment.

    

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