Mechanisms of GPCR Signaling by Membrane Lipids
A growing body of literature from biophysical studies has highlighted the special roles of membrane lipids as endogenous regulators of G protein-coupled receptor (GPCR) signaling. Earlier spectroscopic studies showed GPCRs exist in a function-related equilibrium of simultaneously populated conformers, the relative populations of which are regulated by bound orthosteric drugs. We now present NMR data that show membrane phospholipids and sterols also control this equilibrium with a magnitude comparable to or greater than the influence of drug efficacy with the human class A human GPCR A2AAR. Integrating NMR data with correlative functional assays and molecular modeling allows us to propose a molecular mechanism explaining how lipids influence the formation of GPCR signaling complexes.
Hosted by Professor Andy Nieuwkoop
~Coffee/tea will be served prior to the lecture~