Wednesday, March 14, 2018 at 4:00pm to 5:00pm
Physical Sciences Building, 401
245 East Avenue
Rescheduled to March 14th
Ed Lyman, University of Delaware
Host: Gerald Feigenson
Identifying Loci of Cholesterol Interaction on Integral Membrane Proteins by Molecular Simulation
The G-protein coupled receptors (GPCRs) are an 800 member superfamily of integral membrane proteins that share a common seven transmbrane helix topology, and relay signals in nearly every imaginable physiological context. They are also the target of between 30% and 50% of all clinically approved drugs. As integral membrane proteins, they are responsive to the membrane environment, including cholesterol. Accumulated experimental evidence suggests that there are cholesterol specific binding sites on the membrane facing surface of GPCRs, although direct measurements of cholesterol interactions and functional consequences thereof are limited. Using a combination of molecular dynamics techniques, we predict several cholesterol interaction sites on the surface of the A2A adenosine receptor, a GPCR that regulates excitable tissue and is a target for the treatment of Parkinson’s disease. I will present experimental data from Anne Robinson’s lab (Tulane University) showing cholesterol dependent function of A2A, perhaps mediated by one of these locations. Finally, I will present very recent simulations and analysis of 14 different GPCRs, which show that some of these cholesterol interaction sites are quite common, and others are specific to GPCR subfamilies.