IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v594y2021i7864d10.1038_s41586-021-03641-w.html
   My bibliography  Save this article

Structures of human mGlu2 and mGlu7 homo- and heterodimers

Author

Listed:
  • Juan Du

    (Shanghai Institute of Materia Medica, Chinese Academy of Sciences
    Shanghai Institute of Materia Medica, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Dejian Wang

    (Shanghai Institute of Materia Medica, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Hongcheng Fan

    (University of Chinese Academy of Sciences
    National Center of Protein Science-Beijing, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences)

  • Chanjuan Xu

    (Huazhong University of Science and Technology)

  • Linhua Tai

    (University of Chinese Academy of Sciences
    National Center of Protein Science-Beijing, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences)

  • Shuling Lin

    (Shanghai Institute of Materia Medica, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Shuo Han

    (Shanghai Institute of Materia Medica, Chinese Academy of Sciences)

  • Qiuxiang Tan

    (Shanghai Institute of Materia Medica, Chinese Academy of Sciences)

  • Xinwei Wang

    (Shanghai Institute of Materia Medica, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Tuo Xu

    (Shanghai Institute of Materia Medica, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Hui Zhang

    (Shanghai Institute of Materia Medica, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Xiaojing Chu

    (Shanghai Institute of Materia Medica, Chinese Academy of Sciences)

  • Cuiying Yi

    (Shanghai Institute of Materia Medica, Chinese Academy of Sciences)

  • Peng Liu

    (Huazhong University of Science and Technology)

  • Xiaomei Wang

    (Huazhong University of Science and Technology)

  • Yu Zhou

    (Shanghai Institute of Materia Medica, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Jean-Philippe Pin

    (Université de Montpellier, CNRS, INSERM)

  • Philippe Rondard

    (Université de Montpellier, CNRS, INSERM)

  • Hong Liu

    (Shanghai Institute of Materia Medica, Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    ShanghaiTech University)

  • Jianfeng Liu

    (Huazhong University of Science and Technology
    Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory))

  • Fei Sun

    (University of Chinese Academy of Sciences
    National Center of Protein Science-Beijing, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
    Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory)
    Chinese Academy of Sciences)

  • Beili Wu

    (Shanghai Institute of Materia Medica, Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    ShanghaiTech University)

  • Qiang Zhao

    (Shanghai Institute of Materia Medica, Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

Abstract

The metabotropic glutamate receptors (mGlus) are involved in the modulation of synaptic transmission and neuronal excitability in the central nervous system1. These receptors probably exist as both homo- and heterodimers that have unique pharmacological and functional properties2–4. Here we report four cryo-electron microscopy structures of the human mGlu subtypes mGlu2 and mGlu7, including inactive mGlu2 and mGlu7 homodimers; mGlu2 homodimer bound to an agonist and a positive allosteric modulator; and inactive mGlu2–mGlu7 heterodimer. We observed a subtype-dependent dimerization mode for these mGlus, as a unique dimer interface that is mediated by helix IV (and that is important for limiting receptor activity) exists only in the inactive mGlu2 structure. The structures provide molecular details of the inter- and intra-subunit conformational changes that are required for receptor activation, which distinguish class C G-protein-coupled receptors from those in classes A and B. Furthermore, our structure and functional studies of the mGlu2–mGlu7 heterodimer suggest that the mGlu7 subunit has a dominant role in controlling dimeric association and G-protein activation in the heterodimer. These insights into mGlu homo- and heterodimers highlight the complex landscape of mGlu dimerization and activation.

Suggested Citation

  • Juan Du & Dejian Wang & Hongcheng Fan & Chanjuan Xu & Linhua Tai & Shuling Lin & Shuo Han & Qiuxiang Tan & Xinwei Wang & Tuo Xu & Hui Zhang & Xiaojing Chu & Cuiying Yi & Peng Liu & Xiaomei Wang & Yu Z, 2021. "Structures of human mGlu2 and mGlu7 homo- and heterodimers," Nature, Nature, vol. 594(7864), pages 589-593, June.
  • Handle: RePEc:nat:nature:v:594:y:2021:i:7864:d:10.1038_s41586-021-03641-w
    DOI: 10.1038/s41586-021-03641-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-021-03641-w
    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/s41586-021-03641-w?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. Chris Habrian & Naomi Latorraca & Zhu Fu & Ehud Y. Isacoff, 2023. "Homo- and hetero-dimeric subunit interactions set affinity and efficacy in metabotropic glutamate receptors," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. Kento Ojima & Wataru Kakegawa & Tokiwa Yamasaki & Yuta Miura & Masayuki Itoh & Yukiko Michibata & Ryou Kubota & Tomohiro Doura & Eriko Miura & Hiroshi Nonaka & Seiya Mizuno & Satoru Takahashi & Michis, 2022. "Coordination chemogenetics for activation of GPCR-type glutamate receptors in brain tissue," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Janik B. Hedderich & Margherita Persechino & Katharina Becker & Franziska M. Heydenreich & Torben Gutermuth & Michel Bouvier & Moritz Bünemann & Peter Kolb, 2022. "The pocketome of G-protein-coupled receptors reveals previously untargeted allosteric sites," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. Yaejin Yun & Hyeongseop Jeong & Thibaut Laboute & Kirill A. Martemyanov & Hyung Ho Lee, 2024. "Cryo-EM structure of human class C orphan GPCR GPR179 involved in visual processing," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    5. Kaihua Zhang & Hao Wu & Nicholas Hoppe & Aashish Manglik & Yifan Cheng, 2022. "Fusion protein strategies for cryo-EM study of G protein-coupled receptors," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    6. Pengfei Yan & Xi Lin & Lijie Wu & Lu Xu & Fei Li & Junlin Liu & Fei Xu, 2024. "The binding mechanism of an anti-multiple myeloma antibody to the human GPRC5D homodimer," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    7. Alexa Strauss & Alberto J. Gonzalez-Hernandez & Joon Lee & Nohely Abreu & Purushotham Selvakumar & Leslie Salas-Estrada & Melanie Kristt & Anisul Arefin & Kevin Huynh & Dagan C. Marx & Kristen Gillila, 2024. "Structural basis of positive allosteric modulation of metabotropic glutamate receptor activation and internalization," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    8. Xin Lin & Davide Provasi & Colleen M. Niswender & Wesley B. Asher & Jonathan A. Javitch, 2024. "Elucidating the molecular logic of a metabotropic glutamate receptor heterodimer," Nature Communications, Nature, vol. 15(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:594:y:2021:i:7864:d:10.1038_s41586-021-03641-w. 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.