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

Pressure effects on the conformational equilibrium of the β1-adrenergic receptor

Not scheduled
4h
Harnack House and Henry Ford Building

Harnack House and Henry Ford Building

Board: 2
Poster Posters

Speaker

Dr Layara Abiko (Universität Basel)

Description

G protein-coupled receptors (GPCRs) are versatile chemical sensors, which transmit the signal of an extracellular binding event across the plasma membrane to the intracellular side, leading to the activation of downstream effector proteins.1 This function is achieved via the modulation of a highly dynamical equilibrium of various conformational receptor states.2,3
Despite significant advances in structural and biochemical knowledge on GPCRs, precise atomic details of the receptor dynamics are lacking.
The variation of pressure may change chemical equilibria and kinetics providing information about volume differences between the various states of reactants.4 Here we have probed the effect of pressure on the conformational equilibria of the 15N-valine-labeled β1-adrenergic receptor (β1AR) in various ligand-bound states by solution NMR. The pressure response is ligand-dependent and provides mechanistic insights into GPCR activation.

(1) Alexander, S. P.; Christopoulos, A.; Davenport, A. P.; Kelly, E.; Marrion, N. V.; Peters, J. A.; Faccenda, E.; Harding, S. D.; Pawson, A. J.; Sharman, J. L.; Southan, C.; Davies, J. A. British Journal of Pharmacology 2017, 174, S17.
(2) Nygaard, R.; Zou, Y.; Dror, R. O.; Mildorf, T. J.; Arlow, D. H.; Manglik, A.; Pan, A. C.; Liu, C. W.; Fung, J. J.; Bokoch, M. P.; Thian, F. S.; Kobilka, T. S.; Shaw, D. E.; Mueller, L.; Prosser, R. S.; Kobilka, B. K. Cell 2013, 152 (3), 532.
(3) 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 (7589), 237.
(4) Frauenfelder, H.; Alberding, N. A.; Ansari, A.; Braunstein, D.; Cowen, B. R.; Hong, M. K.; Iben, I. E. T.; Johnson, J. B.; Luck, S. J. Phys. Chem. 1990, 94 (3), 1024.

Primary authors

Dr Layara Abiko (Universität Basel) Dr Anne Grahl (Universität Basel) Prof. Stephan Grzesiek (Universität Basel)

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