Regensburg 2016 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 3: Protein Structure and Dynamics

BP 3.1: Hauptvortrag

Montag, 7. März 2016, 09:30–10:00, H44

Structural Dynamics of Single G-protein Coupled Receptors — •Emmanuel Margeat — Centre de Biochimie Structurale, UMR 5048 CNRS, INSERM U1054, Université de Montpellier, France

Efficient cell-to-cell communication relies on the accurate signaling of cell surface receptors. Understanding the molecular bases of their activation requires the characterization of the dynamic equilibrium between active and resting states. Here, we monitor, using single molecule Förster resonance energy transfer, the kinetics of the activation of metabotropic glutamate receptor (mGluR), a class C G-protein coupled receptor (GPCR) activated by glutamate, the major excitatory neurotransmitter in the central nervous system. By combining filtered Fluorescence Correlation Spectroscopy (fFCS), excited stated lifetime analysis and Photon Distribution (PDA) analysis on single diffusing receptors, we demonstrate that most receptors oscillate between a resting- and an active- conformation on a sub-millisecond timescale. Interestingly, we demonstrate that differences in agonist efficacies stem from differing abilities to shift the conformational equilibrium toward the fully active state, rather than from the stabilization of alternative static conformations, which further highlights the dynamic nature of mGluRs and revises our understanding of receptor activation and allosteric modulation.