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Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5

Author

Listed:
  • Hui Zhang

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

  • Kun Chen

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

  • Qiuxiang Tan

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

  • Qiang Shao

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

  • Shuo Han

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

  • Chenhui Zhang

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

  • Cuiying Yi

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

  • Xiaojing Chu

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

  • Ya Zhu

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

  • Yechun Xu

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

  • Qiang Zhao

    (Shanghai Institute of Materia Medica, Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    Zhongshan Branch, the Institute of Drug Discovery and Development, CAS)

  • 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)

Abstract

The chemokine receptor CCR5 plays a vital role in immune surveillance and inflammation. However, molecular details that govern its endogenous chemokine recognition and receptor activation remain elusive. Here we report three cryo-electron microscopy structures of Gi1 protein-coupled CCR5 in a ligand-free state and in complex with the chemokine MIP-1α or RANTES, as well as the crystal structure of MIP-1α-bound CCR5. These structures reveal distinct binding modes of the two chemokines and a specific accommodate pattern of the chemokine for the distal N terminus of CCR5. Together with functional data, the structures demonstrate that chemokine-induced rearrangement of toggle switch and plasticity of the receptor extracellular region are critical for receptor activation, while a conserved tryptophan residue in helix II acts as a trigger of receptor constitutive activation.

Suggested Citation

  • Hui Zhang & Kun Chen & Qiuxiang Tan & Qiang Shao & Shuo Han & Chenhui Zhang & Cuiying Yi & Xiaojing Chu & Ya Zhu & Yechun Xu & Qiang Zhao & Beili Wu, 2021. "Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24438-5
    DOI: 10.1038/s41467-021-24438-5
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    Cited by:

    1. 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.
    2. Dawei Sun & Yonglian Sun & Eric Janezic & Tricia Zhou & Matthew Johnson & Caleigh Azumaya & Sigrid Noreng & Cecilia Chiu & Akiko Seki & Teresita L. Arenzana & John M. Nicoludis & Yongchang Shi & Baome, 2023. "Structural basis of antibody inhibition and chemokine activation of the human CC chemokine receptor 8," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Robert E. Jefferson & Aurélien Oggier & Andreas Füglistaler & Nicolas Camviel & Mahdi Hijazi & Ana Rico Villarreal & Caroline Arber & Patrick Barth, 2023. "Computational design of dynamic receptor—peptide signaling complexes applied to chemotaxis," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Shankar Raj Devkota & Pramod Aryal & Rina Pokhrel & Wanting Jiao & Andrew Perry & Santosh Panjikar & Richard J. Payne & Matthew C. J. Wilce & Ram Prasad Bhusal & Martin J. Stone, 2023. "Engineering broad-spectrum inhibitors of inflammatory chemokines from subclass A3 tick evasins," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    5. 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.
    6. Daniele Di Marino & Paolo Conflitti & Stefano Motta & Vittorio Limongelli, 2023. "Structural basis of dimerization of chemokine receptors CCR5 and CXCR4," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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