25-30 August 2019
Henry Ford Building
Europe/Berlin timezone

A high-resolution description of functional dynamics and allosteric coupling of the β1-adrenergic receptor from backbone NMR

27 Aug 2019, 11:05
25m
Lecture Hall A (Henry Ford Building)

Lecture Hall A

Henry Ford Building

Talk Dynamics Dynamics

Speaker

Dr Anne Grahl (Biozentrum, University of Basel, Switzerland)

Description

G protein-coupled receptors (GPCRs) are physiologically important transmembrane signaling proteins that elicit intracellular responses upon binding of ligands on the extracellular site. Breakthroughs in crystallography have provided a wealth of static GPCR structures ranging from ligand-bound inactive receptors to fully active receptors in complex with intracellular binding partners such as heterotrimeric G protein and its mimetics. However, dynamical information on the different functional receptor states and their transitions is scarce. Such information is needed to understand the mechanisms of receptor regulation and signal transmission.
We have previously shown that the GPCR response to various ligands can be followed from 1H- 15N resonances at virtually any backbone site in a thermostabilized mutant of the turkey β 1-adrenergic receptor (β 1AR) [1]. We now provide a detailed analysis of populations and dynamics derived from 15N chemical shifts and relaxation rates. For this we used the fully thermostabilized and a more native-like mutant of the receptor in binary complexes ranging from antagonists to agonists as well as in the ternary agonist●G protein mimetic complex. This provides new insights into its activation mechanism and key residues involved in allosteric signal transmission.

[1] Isogai, S., Deupi, X., Opitz, C., Heydenreich, F. M., Tsai, C.-J., Brueckner, F., Schertler, G. F. X., Veprintsev, D. B., Grzesiek, S., Nature 2016, 530, 237–241.

Primary authors

Dr Anne Grahl (Biozentrum, University of Basel, Switzerland) Dr Layara Abiko (Biozentrum, University of Basel, Switzerland) Dr Shin Isogai (Biozentrum, University of Basel, Switzerland) Prof. Stephan Grzesiek (Biozentrum, University of Basel, Switzerland)

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