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How the ubiquitous GPCR receptor family selectively activates signalling pathways

G-protein-coupled receptors activate different G-protein types to trigger divergent signalling pathways. Four structures of receptor–G-protein complexes shed light on this selectivity.
By
  1. Michael J. Capper

    1. Michael J. Capper is in the Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.

  2. Daniel Wacker

    1. Daniel Wacker is in the Department of Pharmacological Sciences and the Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.

About one-third of all drugs, including opioid painkillers, antihistamines and many antipsychotics, target members of a family of proteins called G-protein-coupled receptors (GPCRs)1. This reflects the fact that GPCRs are important in almost all aspects of human physiology, and suggests that many more of them will be promising drug targets for numerous diseases. GPCRs span the cell membrane and convert myriad extracellular signals, including neurotransmitter molecules, hormones, and even light, into a cellular response by activating cellular G proteins and other transducer proteins. Four papers2–5 in this issue help to unravel the mystery of how GPCRs selectively activate a particular group of G proteins known as Gi/o, and provide clues that might aid the design of improved GPCR-targeting drugs.

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Nature 558, 529-530 (2018)

doi: https://doi.org/10.1038/d41586-018-05503-4

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