IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v579y2020i7798d10.1038_s41586-020-1953-1.html
   My bibliography  Save this article

Structure of the neurotensin receptor 1 in complex with β-arrestin 1

Author

Listed:
  • Weijiao Huang

    (Stanford University School of Medicine)

  • Matthieu Masureel

    (Stanford University School of Medicine)

  • Qianhui Qu

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

  • John Janetzko

    (Stanford University School of Medicine)

  • Asuka Inoue

    (Tohoku University)

  • Hideaki E. Kato

    (Stanford University School of Medicine
    The University of Tokyo)

  • Michael J. Robertson

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

  • Khanh C. Nguyen

    (Stanford University)

  • Jeffrey S. Glenn

    (Stanford University)

  • Georgios Skiniotis

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

  • Brian K. Kobilka

    (Stanford University School of Medicine)

Abstract

Arrestin proteins bind to active, phosphorylated G-protein-coupled receptors (GPCRs), thereby preventing G-protein coupling, triggering receptor internalization and affecting various downstream signalling pathways1,2. Although there is a wealth of structural information detailing the interactions between GPCRs and G proteins, less is known about how arrestins engage GPCRs. Here we report a cryo-electron microscopy structure of full-length human neurotensin receptor 1 (NTSR1) in complex with truncated human β-arrestin 1 (βarr1(ΔCT)). We find that phosphorylation of NTSR1 is critical for the formation of a stable complex with βarr1(ΔCT), and identify phosphorylated sites in both the third intracellular loop and the C terminus that may promote this interaction. In addition, we observe a phosphatidylinositol-4,5-bisphosphate molecule forming a bridge between the membrane side of NTSR1 transmembrane segments 1 and 4 and the C-lobe of arrestin. Compared with a structure of a rhodopsin–arrestin-1 complex, in our structure arrestin is rotated by approximately 85° relative to the receptor. These findings highlight both conserved aspects and plasticity among arrestin–receptor interactions.

Suggested Citation

  • Weijiao Huang & Matthieu Masureel & Qianhui Qu & John Janetzko & Asuka Inoue & Hideaki E. Kato & Michael J. Robertson & Khanh C. Nguyen & Jeffrey S. Glenn & Georgios Skiniotis & Brian K. Kobilka, 2020. "Structure of the neurotensin receptor 1 in complex with β-arrestin 1," Nature, Nature, vol. 579(7798), pages 303-308, March.
  • Handle: RePEc:nat:nature:v:579:y:2020:i:7798:d:10.1038_s41586-020-1953-1
    DOI: 10.1038/s41586-020-1953-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-020-1953-1
    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/s41586-020-1953-1?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. 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.
    2. Pankaj Sharma & Elena Maklashina & Markus Voehler & Sona Balintova & Sarka Dvorakova & Michal Kraus & Katerina Hadrava Vanova & Zuzana Nahacka & Renata Zobalova & Stepana Boukalova & Kristyna Cunatova, 2024. "Disordered-to-ordered transitions in assembly factors allow the complex II catalytic subunit to switch binding partners," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Raphael S. Haider & Edda S. F. Matthees & Julia Drube & Mona Reichel & Ulrike Zabel & Asuka Inoue & Andy Chevigné & Cornelius Krasel & Xavier Deupi & Carsten Hoffmann, 2022. "β-arrestin1 and 2 exhibit distinct phosphorylation-dependent conformations when coupling to the same GPCR in living cells," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    4. Amal El Daibani & Joseph M. Paggi & Kuglae Kim & Yianni D. Laloudakis & Petr Popov & Sarah M. Bernhard & Brian E. Krumm & Reid H. J. Olsen & Jeffrey Diberto & F. Ivy Carroll & Vsevolod Katritch & Bern, 2023. "Molecular mechanism of biased signaling at the kappa opioid receptor," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    5. Junke Liu & Hengmin Tang & Chanjuan Xu & Shengnan Zhou & Xunying Zhu & Yuanyuan Li & Laurent Prézeau & Tao Xu & Jean-Philippe Pin & Philippe Rondard & Wei Ji & Jianfeng Liu, 2022. "Biased signaling due to oligomerization of the G protein-coupled platelet-activating factor receptor," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    6. 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.
    7. T. Bertie Ansell & Wanling Song & Claire E. Coupland & Loic Carrique & Robin A. Corey & Anna L. Duncan & C. Keith Cassidy & Maxwell M. G. Geurts & Tim Rasmussen & Andrew B. Ward & Christian Siebold & , 2023. "LipIDens: simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins," Nature Communications, Nature, vol. 14(1), pages 1-14, 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:579:y:2020:i:7798:d:10.1038_s41586-020-1953-1. 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.