G-Protein Coupled Receptors

G-protein coupled receptors (GPCRs) are membrane proteins that are highly dynamical and the targets of many pharmaceutical drugs. GPCRs occupy multiple conformations even in the apo state. Binding of a ligand changes the equilibrium of these states, and therefore the resulting receptor response. We use solution NMR to analyze the dynamical aspects of these conformational landscapes.

 

Our interests are focused on the methyl dynamics of a thermostabilized α1B adrenergic receptor. We produce perdeuterated receptor mutants that remain active in E. coli. Through solution NMR we observe the methyl groups of the isoleucine, leucine and valine side chains. With these methyl probes we aim to elucidate the molecular dynamics of the α1B adrenergic receptor.

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Key references

  • M. Schuster, M. DeLuigi, M. Pantic, S. Vacca, C. Baumann, M. D. Scott, A. Plückthun and O. Zerbe: Optimizing the a1B-Adrenergic Receptor for Solution NMR Studies (2020) BBA Biomembranes, 1862, 183354.

  • L. Kooijman, P. Ansorge, M. Schuster, C. Baumann, F. Löhr, S. Jurt, P. Güntert and O. Zerbe: NMR Backbone and methyl assignment of bacteriorhodopsin incorporated into nanodiscs (2020) J. Biomol. NMR74, 45-60.

  • L. Kooijman, M. Schuster, C. Baumann, S. Jurt, F. Löhr, B. Fürtig, P. Güntert and O. Zerbe,  Dynamics of Bacteriorhodopsin in the Dark-Adapted  State from Solution NMR, Angew. Chem. Int. Ed., DOI:10.1002/anie.202004393.