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Structure insights into selective coupling of G protein subtypes by a class B G protein-coupled receptor

Author

Listed:
  • Li-Hua Zhao

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

  • Jingyu Lin

    (Shandong University)

  • Su-Yu Ji

    (Zhejiang University School of Medicine)

  • X. Edward Zhou

    (Van Andel Research Institute)

  • Chunyou Mao

    (Zhejiang University School of Medicine)

  • Dan-Dan Shen

    (Zhejiang University School of Medicine)

  • Xinheng He

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

  • Peng Xiao

    (Shandong University)

  • Jinpeng Sun

    (Shandong University)

  • Karsten Melcher

    (Van Andel Research Institute)

  • Yan Zhang

    (Zhejiang University School of Medicine
    Zhejiang University Medical Center
    Zhejiang University School of Medicine
    Zhejiang Provincial Key Laboratory of Immunity and Inflammatory diseases)

  • Xiao Yu

    (Shandong University)

  • H. Eric Xu

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

Abstract

The ability to couple with multiple G protein subtypes, such as Gs, Gi/o, or Gq/11, by a given G protein-coupled receptor (GPCR) is critical for many physiological processes. Over the past few years, the cryo-EM structures for all 15 members of the medically important class B GPCRs, all in complex with Gs protein, have been determined. However, no structure of class B GPCRs with Gq/11 has been solved to date, limiting our understanding of the precise mechanisms of G protein coupling selectivity. Here we report the structures of corticotropin releasing factor receptor 2 (CRF2R) bound to Urocortin 1 (UCN1), coupled with different classes of heterotrimeric G proteins, G11 and Go. We compare these structures with the structure of CRF2R in complex with Gs to uncover the structural differences that determine the selective coupling of G protein subtypes by CRF2R. These results provide important insights into the structural basis for the ability of CRF2R to couple with multiple G protein subtypes.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33851-3
    DOI: 10.1038/s41467-022-33851-3
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