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Structural basis of lysophosphatidylserine receptor GPR174 ligand recognition and activation

Author

Listed:
  • Jiale Liang

    (Harbin Institute of Technology)

  • Asuka Inoue

    (Tohoku University)

  • Tatsuya Ikuta

    (Tohoku University)

  • Ruixue Xia

    (Harbin Institute of Technology)

  • Na Wang

    (Harbin Institute of Technology)

  • Kouki Kawakami

    (Tohoku University)

  • Zhenmei Xu

    (Harbin Institute of Technology)

  • Yu Qian

    (Harbin Institute of Technology)

  • Xinyan Zhu

    (Harbin Institute of Technology)

  • Anqi Zhang

    (Harbin Institute of Technology)

  • Changyou Guo

    (Harbin Institute of Technology)

  • Zhiwei Huang

    (Harbin Institute of Technology)

  • Yuanzheng He

    (Harbin Institute of Technology)

Abstract

Lysophosphatidylserine (LysoPS) is a lipid mediator that induces multiple cellular responses through binding to GPR174. Here, we present the cryo-electron microscopy (cryo-EM) structure of LysoPS-bound human GPR174 in complex with Gs protein. The structure reveals a ligand recognition mode, including the negatively charged head group of LysoPS forms extensive polar interactions with surrounding key residues of the ligand binding pocket, and the L-serine moiety buries deeply into a positive charged cavity in the pocket. In addition, the structure unveils a partially open pocket on transmembrane domain helix (TM) 4 and 5 for a lateral entry of ligand. Finally, the structure reveals a Gs engaging mode featured by a deep insertion of a helix 5 (αH5) and extensive polar interactions between receptor and αH5. Taken together, the information revealed by our structural study provides a framework for understanding LysoPS signaling and a rational basis for designing LysoPS receptor-targeting drugs.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36575-0
    DOI: 10.1038/s41467-023-36575-0
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    as
    1. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    2. Xiangli Qu & Na Qiu & Mu Wang & Bingjie Zhang & Juan Du & Zhiwei Zhong & Wei Xu & Xiaojing Chu & Limin Ma & Cuiying Yi & Shuo Han & Wenqing Shui & Qiang Zhao & Beili Wu, 2022. "Structural basis of tethered agonism of the adhesion GPCRs ADGRD1 and ADGRF1," Nature, Nature, vol. 604(7907), pages 779-785, April.
    3. 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.
    4. 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.
    5. Xi Lin & Mingyue Li & Niandong Wang & Yiran Wu & Zhipu Luo & Shimeng Guo & Gye-Won Han & Shaobai Li & Yang Yue & Xiaohu Wei & Xin Xie & Yong Chen & Suwen Zhao & Jian Wu & Ming Lei & Fei Xu, 2020. "Structural basis of ligand recognition and self-activation of orphan GPR52," Nature, Nature, vol. 579(7797), pages 152-157, March.
    6. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    7. Shian Liu & Navid Paknejad & Lan Zhu & Yasuyuki Kihara & Manisha Ray & Jerold Chun & Wei Liu & Richard K. Hite & Xin-Yun Huang, 2022. "Differential activation mechanisms of lipid GPCRs by lysophosphatidic acid and sphingosine 1-phosphate," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    8. Reiya Taniguchi & Asuka Inoue & Misa Sayama & Akiharu Uwamizu & Keitaro Yamashita & Kunio Hirata & Masahito Yoshida & Yoshiki Tanaka & Hideaki E. Kato & Yoshiko Nakada-Nakura & Yuko Otani & Tomohiro N, 2017. "Structural insights into ligand recognition by the lysophosphatidic acid receptor LPA6," Nature, Nature, vol. 548(7667), pages 356-360, August.
    9. 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.
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    1. Yingying Nie & Zeming Qiu & Sijia Chen & Zhao Chen & Xiaocui Song & Yan Ma & Niu Huang & Jason G. Cyster & Sanduo Zheng, 2023. "Specific binding of GPR174 by endogenous lysophosphatidylserine leads to high constitutive Gs signaling," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Tamaki Izume & Ryo Kawahara & Akiharu Uwamizu & Luying Chen & Shun Yaginuma & Jumpei Omi & Hiroki Kawana & Fengjue Hou & Fumiya K. Sano & Tatsuki Tanaka & Kazuhiro Kobayashi & Hiroyuki H. Okamoto & Yo, 2024. "Structural basis for lysophosphatidylserine recognition by GPR34," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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