Membrane Mimetic-Dependence of GPCR Energy Landscapes.

ABSTRACT: Protein function strongly depends on temperature, which is related to temperature-dependent changes in the equilibria of protein conformational states. We leveraged variable-temperature ¹⁹F-NMR spectroscopy to interrogate the temperature dependence of the conformational landscape of the human A_2A adenosine receptor (A_2AAR), a class A GPCR. Temperature-induced changes in the conformational equilibria of A_2AAR in lipid nanodiscs were markedly dependent on the efficacy of bound drugs. While antagonist complexes displayed only modest changes as the temperature rose, both full and partial agonist complexes exhibited substantial increases in the active state population. Importantly, the temperature-dependent response of complexes with both full and par

SUBMITTER: Thakur N 

PROVIDER: S-EPMC10614885 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature