Science Signaling Podcast for 3 November 2015: Ligands control GPCR voltage sensitivity

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Science Signaling  03 Nov 2015:
Vol. 8, Issue 401, pp. pc27
DOI: 10.1126/scisignal.aad6787

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This Podcast features an interview with Moritz Bünemann and Peter Kolb, authors of a Research Article that appears in the 3 November 2015 issue of Science Signaling, about how the mode of ligand binding to a voltage-sensitive G protein–coupled receptor (GPCR) determines whether changes in membrane potential enhance or attenuate signaling. Signaling by most GPCRs is primarily controlled by the binding of ligands to the receptors, but some GPCRs are also sensitive to changes in membrane potential. Muscarinic acetylcholine receptors are voltage-sensitive GPCRs that bind various ligands. Rinne et al. found that membrane depolarization enhanced signaling by the M3 muscarinic acetylcholine receptor when the receptor was bound to some agonists but attenuated signaling when the receptor was bound to other agonists. These two groups of agonists adopted distinct orientations within the ligand-binding pocket of the receptor. Whether membrane depolarization enhanced or attenuated signaling depended on the orientation of the agonist within the binding pocket.

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