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Common drugs initiate a molecular pas de quatre at the surface of the cell membrane
Date:7/26/2011

Brussels, 25 July 2011 - G protein-coupled receptors (GPCRs) are popular drug targets, accounting for about one-third of approved drugs and many hundreds of drugs currently in development. They act as molecular switches that transduce extracellular signals by activating heterotrimeric G proteins (G proteins) located at the inside of the cell. Changes in shape of these proteins determine essential processes, including whether an eye detects light, a virus invades a cell or a drug slows a racing heart. GPCRs sit in the membranes of cells throughout the body. They pick up signals from outside the body such as odors, flavors or light and signals from within the body, such as neurotransmitters or hormones. Once those signals are transmitted to the inside of the cell, they activate intracellular G proteins, triggering a variety of biochemical pathways. Despite their importance in biology and medicine, the way G protein-coupled receptors couple the detection of a signals from the outside world to the activation of the G-protein at the inside of the cell has remained largely unknown an important obstacle to understanding their function.

In an article in Nature, scientists from Stanford University, University of Wisconsin and VIB-Vrije Universiteit Brussel now reveal the complete three-dimensional atomic structure of an activated GPCR the beta-2 adrenergic receptor (beta-2AR) in a complex with its G protein. This is an important step towards the understanding of how the receptors actually work.

Beta-2 AR is activated by the hormones adrenaline and noradrenaline. Activation of the receptor lies at the basis of the body's fight-or-flight response by speeding up the heart, increasing blood pressure and opening airways. As a result, it is a key target for anti-asthma and blood pressure medications.

Adrenaline binds from the outside of the cell to the adrenergic receptor that is embedded in the cellular membrane, causing the heterotrimer
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Contact: Joris Gansemans
info@vib.be
32-924-46611
VIB (the Flanders Institute for Biotechnology)
Source:Eurekalert

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