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Structural basis for the activation and ligand recognition of the human oxytocin receptor

Author

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  • Yann Waltenspühl

    (University of Zürich
    Novo Nordisk A/S)

  • Janosch Ehrenmann

    (University of Zürich
    leadXpro AG, PARK innovAARE)

  • Santiago Vacca

    (University of Zürich)

  • Cristian Thom

    (University of Zürich)

  • Ohad Medalia

    (University of Zürich)

  • Andreas Plückthun

    (University of Zürich)

Abstract

The small cyclic neuropeptide hormone oxytocin (OT) and its cognate receptor play a central role in the regulation of social behaviour and sexual reproduction. Here we report the single-particle cryo-electron microscopy structure of the active oxytocin receptor (OTR) in complex with its cognate ligand oxytocin. Our structure provides high-resolution insights into the OT binding mode, the OTR activation mechanism as well as the subtype specificity within the oxytocin/vasopressin receptor family.

Suggested Citation

  • Yann Waltenspühl & Janosch Ehrenmann & Santiago Vacca & Cristian Thom & Ohad Medalia & Andreas Plückthun, 2022. "Structural basis for the activation and ligand recognition of the human oxytocin receptor," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31325-0
    DOI: 10.1038/s41467-022-31325-0
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    1. Shoji Maeda & Antoine Koehl & Hugues Matile & Hongli Hu & Daniel Hilger & Gebhard F. X. Schertler & Aashish Manglik & Georgios Skiniotis & Roger J. P. Dawson & Brian K. Kobilka, 2018. "Development of an antibody fragment that stabilizes GPCR/G-protein complexes," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    2. David Jonathan Wasilko & Zachary Lee Johnson & Mark Ammirati & Ye Che & Matthew C. Griffor & Seungil Han & Huixian Wu, 2020. "Structural basis for chemokine receptor CCR6 activation by the endogenous protein ligand CCL20," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    3. Chuan Hong & Noel J. Byrne & Beata Zamlynny & Srivanya Tummala & Li Xiao & Jennifer M. Shipman & Andrea T. Partridge & Christina Minnick & Michael J. Breslin & Michael T. Rudd & Shawn J. Stachel & Van, 2021. "Structures of active-state orexin receptor 2 rationalize peptide and small-molecule agonist recognition and receptor activation," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
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