IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v572y2019i7767d10.1038_s41586-019-1337-6.html
   My bibliography  Save this article

Conformational transitions of a neurotensin receptor 1–Gi1 complex

Author

Listed:
  • Hideaki E. Kato

    (Stanford University School of Medicine
    The University of Tokyo)

  • Yan Zhang

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Zhejiang University School of Medicine)

  • Hongli Hu

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Carl-Mikael Suomivuori

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University
    Stanford University)

  • Francois Marie Ngako Kadji

    (Tohoku University)

  • Junken Aoki

    (Tohoku University)

  • Kaavya Krishna Kumar

    (Stanford University School of Medicine)

  • Rasmus Fonseca

    (Stanford University School of Medicine
    Stanford University School of Medicine
    University of Copenhagen)

  • Daniel Hilger

    (Stanford University School of Medicine)

  • Weijiao Huang

    (Stanford University School of Medicine)

  • Naomi R. Latorraca

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University
    Stanford University)

  • Asuka Inoue

    (Tohoku University)

  • Ron O. Dror

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Stanford University
    Stanford University)

  • Brian K. Kobilka

    (Stanford University School of Medicine)

  • Georgios Skiniotis

    (Stanford University School of Medicine
    Stanford University School of Medicine)

Abstract

Neurotensin receptor 1 (NTSR1) is a G-protein-coupled receptor (GPCR) that engages multiple subtypes of G protein, and is involved in the regulation of blood pressure, body temperature, weight and the response to pain. Here we present structures of human NTSR1 in complex with the agonist JMV449 and the heterotrimeric Gi1 protein, at a resolution of 3 Å. We identify two conformations: a canonical-state complex that is similar to recently reported GPCR–Gi/o complexes (in which the nucleotide-binding pocket adopts more flexible conformations that may facilitate nucleotide exchange), and a non-canonical state in which the G protein is rotated by about 45 degrees relative to the receptor and exhibits a more rigid nucleotide-binding pocket. In the non-canonical state, NTSR1 exhibits features of both active and inactive conformations, which suggests that the structure may represent an intermediate form along the activation pathway of G proteins. This structural information, complemented by molecular dynamics simulations and functional studies, provides insights into the complex process of G-protein activation.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:nature:v:572:y:2019:i:7767:d:10.1038_s41586-019-1337-6
    DOI: 10.1038/s41586-019-1337-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-019-1337-6
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/s41586-019-1337-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Heng Liu & Dapeng Sun & Alexander Myasnikov & Marjorie Damian & Jean-Louis Baneres & Ji Sun & Cheng Zhang, 2021. "Structural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamoren," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    2. Wenli Zhao & Wenru Zhang & Mu Wang & Minmin Lu & Shutian Chen & Tingting Tang & Gisela Schnapp & Holger Wagner & Albert Brennauer & Cuiying Yi & Xiaojing Chu & Shuo Han & Beili Wu & Qiang Zhao, 2022. "Ligand recognition and activation of neuromedin U receptor 2," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    3. Chunyou Mao & Mengru Gao & Shao-Kun Zang & Yanqing Zhu & Dan-Dan Shen & Li-Nan Chen & Liu Yang & Zhiwei Wang & Huibing Zhang & Wei-Wei Wang & Qingya Shen & Yanhui Lu & Xin Ma & Yan Zhang, 2023. "Orthosteric and allosteric modulation of human HCAR2 signaling complex," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    4. Mark J. Wall & Emily Hill & Robert Huckstepp & Kerry Barkan & Giuseppe Deganutti & Michele Leuenberger & Barbara Preti & Ian Winfield & Sabrina Carvalho & Anna Suchankova & Haifeng Wei & Dewi Safitri , 2022. "Selective activation of Gαob by an adenosine A1 receptor agonist elicits analgesia without cardiorespiratory depression," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    5. Fabian Bumbak & James B. Bower & Skylar C. Zemmer & Asuka Inoue & Miquel Pons & Juan Carlos Paniagua & Fei Yan & James Ford & Hongwei Wu & Scott A. Robson & Ross A. D. Bathgate & Daniel J. Scott & Pau, 2023. "Stabilization of pre-existing neurotensin receptor conformational states by β-arrestin-1 and the biased allosteric modulator ML314," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    6. Manbir Sandhu & Aaron Cho & Ning Ma & Elizaveta Mukhaleva & Yoon Namkung & Sangbae Lee & Soumadwip Ghosh & John H. Lee & David E. Gloriam & Stéphane A. Laporte & M. Madan Babu & Nagarajan Vaidehi, 2022. "Dynamic spatiotemporal determinants modulate GPCR:G protein coupling selectivity and promiscuity," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    7. Jinkang Shen & Dongqi Zhang & Yao Fu & Anqi Chen & Xiaoli Yang & Haitao Zhang, 2022. "Cryo-EM structures of human bradykinin receptor-Gq proteins complexes," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    8. Na Wang & Xinheng He & Jing Zhao & Hualiang Jiang & Xi Cheng & Yu Xia & H. Eric Xu & Yuanzheng He, 2022. "Structural basis of leukotriene B4 receptor 1 activation," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    9. Xiuwen Zhai & Chunyou Mao & Qingya Shen & Shaokun Zang & Dan-Dan Shen & Huibing Zhang & Zhaohong Chen & Gang Wang & Changming Zhang & Yan Zhang & Zhihong Liu, 2022. "Molecular insights into the distinct signaling duration for the peptide-induced PTH1R activation," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    10. Hiroaki Akasaka & Tatsuki Tanaka & Fumiya K. Sano & Yuma Matsuzaki & Wataru Shihoya & Osamu Nureki, 2022. "Structure of the active Gi-coupled human lysophosphatidic acid receptor 1 complexed with a potent agonist," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    11. Youwen Zhuang & Lei Wang & Jia Guo & Dapeng Sun & Yue Wang & Weiyi Liu & H. Eric Xu & Cheng Zhang, 2022. "Molecular recognition of formylpeptides and diverse agonists by the formylpeptide receptors FPR1 and FPR2," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    12. Chongzhao You & Yumu Zhang & Peiyu Xu & Sijie Huang & Wanchao Yin & H. Eric Xu & Yi Jiang, 2022. "Structural insights into the peptide selectivity and activation of human neuromedin U receptors," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    13. Jun Xu & Qinggong Wang & Harald Hübner & Yunfei Hu & Xiaogang Niu & Haoqing Wang & Shoji Maeda & Asuka Inoue & Yuyong Tao & Peter Gmeiner & Yang Du & Changwen Jin & Brian K. Kobilka, 2023. "Structural and dynamic insights into supra-physiological activation and allosteric modulation of a muscarinic acetylcholine receptor," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    14. 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.
    15. Yan Chen & Qingtong Zhou & Jiang Wang & Youwei Xu & Yun Wang & Jiahui Yan & Yibing Wang & Qi Zhu & Fenghui Zhao & Chenghao Li & Chuan-Wei Chen & Xiaoqing Cai & Ross A .D. Bathgate & Chun Shen & H. Eri, 2023. "Ligand recognition mechanism of the human relaxin family peptide receptor 4 (RXFP4)," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:572:y:2019:i:7767:d:10.1038_s41586-019-1337-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.