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Structural basis of neuropeptide Y signaling through Y1 receptor

Author

Listed:
  • Chaehee Park

    (Seoul National University)

  • Jinuk Kim

    (Seoul National University)

  • Seung-Bum Ko

    (Seoul National University)

  • Yeol Kyo Choi

    (Lehigh University)

  • Hyeongseop Jeong

    (Korea Basic Science Institute)

  • Hyeonuk Woo

    (Seoul National University)

  • Hyunook Kang

    (Seoul National University)

  • Injin Bang

    (Seoul National University
    New York University School of Medicine)

  • Sang Ah Kim

    (Seoul National University
    Seoul National University)

  • Tae-Young Yoon

    (Seoul National University
    Seoul National University)

  • Chaok Seok

    (Seoul National University)

  • Wonpil Im

    (Lehigh University)

  • Hee-Jung Choi

    (Seoul National University)

Abstract

Neuropeptide Y (NPY) is highly abundant in the brain and involved in various physiological processes related to food intake and anxiety, as well as human diseases such as obesity and cancer. However, the molecular details of the interactions between NPY and its receptors are poorly understood. Here, we report a cryo-electron microscopy structure of the NPY-bound neuropeptide Y1 receptor (Y1R) in complex with Gi1 protein. The NPY C-terminal segment forming the extended conformation binds deep into the Y1R transmembrane core, where the amidated C-terminal residue Y36 of NPY is located at the base of the ligand-binding pocket. Furthermore, the helical region and two N-terminal residues of NPY interact with Y1R extracellular loops, contributing to the high affinity of NPY for Y1R. The structural analysis of NPY-bound Y1R and mutagenesis studies provide molecular insights into the activation mechanism of Y1R upon NPY binding.

Suggested Citation

  • Chaehee Park & Jinuk Kim & Seung-Bum Ko & Yeol Kyo Choi & Hyeongseop Jeong & Hyeonuk Woo & Hyunook Kang & Injin Bang & Sang Ah Kim & Tae-Young Yoon & Chaok Seok & Wonpil Im & Hee-Jung Choi, 2022. "Structural basis of neuropeptide Y signaling through Y1 receptor," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28510-6
    DOI: 10.1038/s41467-022-28510-6
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    as
    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. Maoqing Dong & Giuseppe Deganutti & Sarah J. Piper & Yi-Lynn Liang & Maryam Khoshouei & Matthew J. Belousoff & Kaleeckal G. Harikumar & Christopher A. Reynolds & Alisa Glukhova & Sebastian G. B. Furne, 2020. "Structure and dynamics of the active Gs-coupled human secretin receptor," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    3. Wataru Shihoya & Tamaki Izume & Asuka Inoue & Keitaro Yamashita & Francois Marie Ngako Kadji & Kunio Hirata & Junken Aoki & Tomohiro Nishizawa & Osamu Nureki, 2018. "Crystal structures of human ETB receptor provide mechanistic insight into receptor activation and partial activation," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    4. Satinder Kaur & Josue Gomez-Blanco & Ahmad A. Z. Khalifa & Swathi Adinarayanan & Ruben Sanchez-Garcia & Daniel Wrapp & Jason S. McLellan & Khanh Huy Bui & Javier Vargas, 2021. "Local computational methods to improve the interpretability and analysis of cryo-EM maps," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    5. Hideaki E. Kato & Yan Zhang & Hongli Hu & Carl-Mikael Suomivuori & Francois Marie Ngako Kadji & Junken Aoki & Kaavya Krishna Kumar & Rasmus Fonseca & Daniel Hilger & Weijiao Huang & Naomi R. Latorraca, 2019. "Conformational transitions of a neurotensin receptor 1–Gi1 complex," Nature, Nature, vol. 572(7767), pages 80-85, August.
    6. Yanyong Kang & Oleg Kuybeda & Parker W. de Waal & Somnath Mukherjee & Ned Van Eps & Przemyslaw Dutka & X. Edward Zhou & Alberto Bartesaghi & Satchal Erramilli & Takefumi Morizumi & Xin Gu & Yanting Yi, 2018. "Publisher Correction: Cryo-EM structure of human rhodopsin bound to an inhibitory G protein," Nature, Nature, vol. 561(7724), pages 44-44, September.
    7. 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.
    8. Zhenlin Yang & Shuo Han & Max Keller & Anette Kaiser & Brian J. Bender & Mathias Bosse & Kerstin Burkert & Lisa M. Kögler & David Wifling & Guenther Bernhardt & Nicole Plank & Timo Littmann & Peter Sc, 2018. "Structural basis of ligand binding modes at the neuropeptide Y Y1 receptor," Nature, Nature, vol. 556(7702), pages 520-524, April.
    9. Yanyong Kang & Oleg Kuybeda & Parker W. de Waal & Somnath Mukherjee & Ned Van Eps & Przemyslaw Dutka & X. Edward Zhou & Alberto Bartesaghi & Satchal Erramilli & Takefumi Morizumi & Xin Gu & Yanting Yi, 2018. "Cryo-EM structure of human rhodopsin bound to an inhibitory G protein," Nature, Nature, vol. 558(7711), pages 553-558, June.
    10. Antoine Koehl & Hongli Hu & Shoji Maeda & Yan Zhang & Qianhui Qu & Joseph M. Paggi & Naomi R. Latorraca & Daniel Hilger & Roger Dawson & Hugues Matile & Gebhard F. X. Schertler & Sebastien Granier & W, 2018. "Structure of the µ-opioid receptor–Gi protein complex," Nature, Nature, vol. 558(7711), pages 547-552, June.
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