IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-17933-8.html
   My bibliography  Save this article

Cryo-EM structure of an activated VIP1 receptor-G protein complex revealed by a NanoBiT tethering strategy

Author

Listed:
  • Jia Duan

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Dan-dan Shen

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

  • X. Edward Zhou

    (Van Andel Institute)

  • Peng Bi

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

  • Qiu-feng Liu

    (Chinese Academy of Sciences)

  • Yang-xia Tan

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    ShanghaiTech University)

  • You-wen Zhuang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Hui-bing Zhang

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

  • Pei-yu Xu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Si-Jie Huang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    ShanghaiTech University)

  • Shan-shan Ma

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Xin-heng He

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Karsten Melcher

    (Van Andel Institute)

  • Yan Zhang

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

  • H. Eric Xu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    ShanghaiTech University)

  • Yi Jiang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

Abstract

Vasoactive intestinal polypeptide receptor (VIP1R) is a widely expressed class B G protein-coupled receptor and a drug target for the treatment of neuronal, metabolic, and inflammatory diseases. However, our understanding of its mechanism of action and the potential of drug discovery targeting this receptor is limited by the lack of structural information of VIP1R. Here we report a cryo-electron microscopy structure of human VIP1R bound to PACAP27 and Gs heterotrimer, whose complex assembly is stabilized by a NanoBiT tethering strategy. Comparison with other class B GPCR structures reveals that PACAP27 engages VIP1R with its N-terminus inserting into the ligand binding pocket at the transmembrane bundle of the receptor, which subsequently couples to the G protein in a receptor-specific manner. This structure has provided insights into the molecular basis of PACAP27 binding and VIP receptor activation. The methodology of the NanoBiT tethering may help to provide structural information of unstable complexes.

Suggested Citation

  • Jia Duan & Dan-dan Shen & X. Edward Zhou & Peng Bi & Qiu-feng Liu & Yang-xia Tan & You-wen Zhuang & Hui-bing Zhang & Pei-yu Xu & Si-Jie Huang & Shan-shan Ma & Xin-heng He & Karsten Melcher & Yan Zhang, 2020. "Cryo-EM structure of an activated VIP1 receptor-G protein complex revealed by a NanoBiT tethering strategy," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17933-8
    DOI: 10.1038/s41467-020-17933-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-17933-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-17933-8?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
    ---><---

    Citations

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


    Cited by:

    1. Dohyun Im & Jun-ichi Kishikawa & Yuki Shiimura & Hiromi Hisano & Akane Ito & Yoko Fujita-Fujiharu & Yukihiko Sugita & Takeshi Noda & Takayuki Kato & Hidetsugu Asada & So Iwata, 2023. "Structural insights into the agonists binding and receptor selectivity of human histamine H4 receptor," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    2. Fenghui Zhao & Qingtong Zhou & Zhaotong Cong & Kaini Hang & Xinyu Zou & Chao Zhang & Yan Chen & Antao Dai & Anyi Liang & Qianqian Ming & Mu Wang & Li-Nan Chen & Peiyu Xu & Rulve Chang & Wenbo Feng & T, 2022. "Structural insights into multiplexed pharmacological actions of tirzepatide and peptide 20 at the GIP, GLP-1 or glucagon receptors," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Canrong Wu & Youwei Xu & Qian He & Dianrong Li & Jia Duan & Changyao Li & Chongzhao You & Han Chen & Weiliang Fan & Yi Jiang & H. Eric Xu, 2023. "Ligand-induced activation and G protein coupling of prostaglandin F2α receptor," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    4. 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.
    5. Jia Duan & Dan-Dan Shen & Tingting Zhao & Shimeng Guo & Xinheng He & Wanchao Yin & Peiyu Xu & Yujie Ji & Li-Nan Chen & Jinyu Liu & Huibing Zhang & Qiufeng Liu & Yi Shi & Xi Cheng & Hualiang Jiang & H., 2022. "Molecular basis for allosteric agonism and G protein subtype selectivity of galanin receptors," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    6. Yu Qian & Zhengxiong Ma & Zhenmei Xu & Yaning Duan & Yangjie Xiong & Ruixue Xia & Xinyan Zhu & Zongwei Zhang & Xinyu Tian & Han Yin & Jian Liu & Jing Song & Yang Lu & Anqi Zhang & Changyou Guo & Lihua, 2024. "Structural basis of Frizzled 4 in recognition of Dishevelled 2 unveils mechanism of WNT signaling activation," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    7. Xinyan Zhu & Yu Qian & Xiaowan Li & Zhenmei Xu & Ruixue Xia & Na Wang & Jiale Liang & Han Yin & Anqi Zhang & Changyou Guo & Guangfu Wang & Yuanzheng He, 2022. "Structural basis of adhesion GPCR GPR110 activation by stalk peptide and G-proteins coupling," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    8. Yingna Xu & Wenbo Feng & Qingtong Zhou & Anyi Liang & Jie Li & Antao Dai & Fenghui Zhao & Jiahui Yan & Chuan-Wei Chen & Hao Li & Li-Hua Zhao & Tian Xia & Yi Jiang & H. Eric Xu & Dehua Yang & Ming-Wei , 2022. "A distinctive ligand recognition mechanism by the human vasoactive intestinal polypeptide receptor 2," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    9. Li-Hua Zhao & Jingyu Lin & Su-Yu Ji & X. Edward Zhou & Chunyou Mao & Dan-Dan Shen & Xinheng He & Peng Xiao & Jinpeng Sun & Karsten Melcher & Yan Zhang & Xiao Yu & H. Eric Xu, 2022. "Structure insights into selective coupling of G protein subtypes by a class B G protein-coupled receptor," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    10. 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.
    11. Shota Suzuki & Kotaro Tanaka & Kouki Nishikawa & Hiroshi Suzuki & Atsunori Oshima & Yoshinori Fujiyoshi, 2023. "Structural basis of hydroxycarboxylic acid receptor signaling mechanisms through ligand binding," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    12. Yujie Ji & Jia Duan & Qingning Yuan & Xinheng He & Gong Yang & Shengnan Zhu & Kai Wu & Wen Hu & Tianyu Gao & Xi Cheng & Hualiang Jiang & H. Eric Xu & Yi Jiang, 2023. "Structural basis of peptide recognition and activation of endothelin receptors," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    13. Hongmin Cai & Shimeng Guo & Youwei Xu & Jun Sun & Junrui Li & Zhikan Xia & Yi Jiang & Xin Xie & H. Eric Xu, 2024. "Cryo-EM structures of adenosine receptor A3AR bound to selective agonists," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    14. Xuan Zhang & Yujing Wang & Shreyas Supekar & Xu Cao & Jingkai Zhou & Jessica Dang & Siqi Chen & Laura Jenkins & Sara Marsango & Xiu Li & Guibing Liu & Graeme Milligan & Mingye Feng & Hao Fan & Weimin , 2023. "Pro-phagocytic function and structural basis of GPR84 signaling," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    15. 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.
    16. Ruixue Xia & Shuang Shi & Zhenmei Xu & Henry F. Vischer & Albert D. Windhorst & Yu Qian & Yaning Duan & Jiale Liang & Kai Chen & Anqi Zhang & Changyou Guo & Rob Leurs & Yuanzheng He, 2024. "Structural basis of ligand recognition and design of antihistamines targeting histamine H4 receptor," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    17. 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.
    18. Jiale Liang & Asuka Inoue & Tatsuya Ikuta & Ruixue Xia & Na Wang & Kouki Kawakami & Zhenmei Xu & Yu Qian & Xinyan Zhu & Anqi Zhang & Changyou Guo & Zhiwei Huang & Yuanzheng He, 2023. "Structural basis of lysophosphatidylserine receptor GPR174 ligand recognition and activation," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    19. Sarah J. Piper & Giuseppe Deganutti & Jessica Lu & Peishen Zhao & Yi-Lynn Liang & Yao Lu & Madeleine M. Fletcher & Mohammed Akhter Hossain & Arthur Christopoulos & Christopher A. Reynolds & Radostin D, 2022. "Understanding VPAC receptor family peptide binding and selectivity," Nature Communications, Nature, vol. 13(1), pages 1-20, 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:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17933-8. 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.