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A modulator-bound GPCR structure enables allosteric non-opioid analgesia

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Structural studies of a positive allosteric modulator of the adenosine A1 receptor demonstrate the mechanisms by which stabilization of the GPCR–G protein complex bound to its endogenous agonist yields analgesic efficacy in an animal model of neuropathic pain.

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Fig. 1: Allosteric modulation of the A1R promotes agonist–A1R–PAM–G protein complex stability and analgesia in a disease-state-specific manner.

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Acknowledgements

G.S. is a New York Stem Cell Foundation – Robertson Investigator. We thank Joshua Blair for editing the manuscript.

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Authors and Affiliations

  1. Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    David F. Lee, Matan Geron & Grégory Scherrer

  2. UNC Neuroscience Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    David F. Lee, Matan Geron & Grégory Scherrer

  3. Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    David F. Lee, Matan Geron & Grégory Scherrer

  4. Pharmacology Curriculum, Biological & Biomedical Sciences Program, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    David F. Lee

  5. New York Stem Cell Foundation–Robertson Investigator, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Grégory Scherrer

Authors
  1. David F. Lee
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  2. Matan Geron
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  3. Grégory Scherrer
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Correspondence to Grégory Scherrer.

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Lee, D.F., Geron, M. & Scherrer, G. A modulator-bound GPCR structure enables allosteric non-opioid analgesia. Nat Struct Mol Biol 28, 871–872 (2021). https://doi.org/10.1038/s41594-021-00681-8

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