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Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor–Gs complex

Author

Listed:
  • Yi-Lynn Liang

    (Monash Institute of Pharmaceutical Sciences, Monash University)

  • Maryam Khoshouei

    (Max Planck Institute of Biochemistry)

  • Alisa Glukhova

    (Monash Institute of Pharmaceutical Sciences, Monash University)

  • Sebastian G. B. Furness

    (Monash Institute of Pharmaceutical Sciences, Monash University)

  • Peishen Zhao

    (Monash Institute of Pharmaceutical Sciences, Monash University)

  • Lachlan Clydesdale

    (Monash Institute of Pharmaceutical Sciences, Monash University)

  • Cassandra Koole

    (Monash Institute of Pharmaceutical Sciences, Monash University)

  • Tin T. Truong

    (Monash Institute of Pharmaceutical Sciences, Monash University)

  • David M. Thal

    (Monash Institute of Pharmaceutical Sciences, Monash University)

  • Saifei Lei

    (University of Chinese Academy of Sciences
    The National Center for Drug Screening and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences)

  • Mazdak Radjainia

    (Monash Institute of Pharmaceutical Sciences, Monash University
    FEI)

  • Radostin Danev

    (Max Planck Institute of Biochemistry)

  • Wolfgang Baumeister

    (Max Planck Institute of Biochemistry)

  • Ming-Wei Wang

    (University of Chinese Academy of Sciences
    The National Center for Drug Screening and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
    School of Pharmacy, Fudan University)

  • Laurence J. Miller

    (Monash Institute of Pharmaceutical Sciences, Monash University
    Mayo Clinic)

  • Arthur Christopoulos

    (Monash Institute of Pharmaceutical Sciences, Monash University)

  • Patrick M. Sexton

    (Monash Institute of Pharmaceutical Sciences, Monash University
    School of Pharmacy, Fudan University)

  • Denise Wootten

    (Monash Institute of Pharmaceutical Sciences, Monash University)

Abstract

The structure of the glucagon-like peptide 1 receptor (GLP-1R) with its biased agonist exendin-P5 sheds light on both receptor activation and the mechanism of biased agonism.

Suggested Citation

  • Yi-Lynn Liang & Maryam Khoshouei & Alisa Glukhova & Sebastian G. B. Furness & Peishen Zhao & Lachlan Clydesdale & Cassandra Koole & Tin T. Truong & David M. Thal & Saifei Lei & Mazdak Radjainia & Rado, 2018. "Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor–Gs complex," Nature, Nature, vol. 555(7694), pages 121-125, March.
    • Handle: RePEc:nat:nature:v:555:y:2018:i:7694:d:10.1038_nature25773
    DOI: 10.1038/nature25773
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    Citations

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    Cited by:

    1. Kaleeckal G. Harikumar & Sarah J. Piper & Arthur Christopoulos & Denise Wootten & Patrick M. Sexton & Laurence J. Miller, 2024. "Impact of secretin receptor homo-dimerization on natural ligand binding," Nature Communications, Nature, vol. 15(1), pages 1-12, 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. Yuxia Qian & Jiening Wang & Linlin Yang & Yanru Liu & Lina Wang & Wei Liu & Yun Lin & Hong Yang & Lixin Ma & Sheng Ye & Shan Wu & Anna Qiao, 2022. "Activation and signaling mechanism revealed by GPR119-Gs complex structures," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    4. Kevin M. Knight & Brian E. Krumm & Nicholas J. Kapolka & W. Grant Ludlam & Meng Cui & Sepehr Mani & Iya Prytkova & Elizabeth G. Obarow & Tyler J. Lefevre & Wenyuan Wei & Ning Ma & Xi-Ping Huang & Jona, 2024. "A neurodevelopmental disorder mutation locks G proteins in the transitory pre-activated state," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    5. 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.
    6. Xudong Wang & Chris Neale & Soo-Kyung Kim & William A. Goddard & Libin Ye, 2023. "Intermediate-state-trapped mutants pinpoint G protein-coupled receptor conformational allostery," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    7. Yong-Seok Kim & Jun-Hee Yeon & Woori Ko & Byung-Chang Suh, 2023. "Two-step structural changes in M3 muscarinic receptor activation rely on the coupled Gq protein cycle," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    8. 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.
    9. 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.
    10. 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.

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