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Allosteric coupling from G protein to the agonist-binding pocket in GPCRs

Author

Listed:
  • Brian T. DeVree

    (University of Michigan Medical School)

  • Jacob P. Mahoney

    (University of Michigan Medical School)

  • Gisselle A. Vélez-Ruiz

    (University of Michigan Medical School)

  • Soren G. F. Rasmussen

    (Stanford University)

  • Adam J. Kuszak

    (University of Michigan Medical School)

  • Elin Edwald

    (University of Michigan Medical School)

  • Juan-Jose Fung

    (Stanford University)

  • Aashish Manglik

    (Stanford University)

  • Matthieu Masureel

    (Stanford University)

  • Yang Du

    (Stanford University)

  • Rachel A. Matt

    (Stanford University)

  • Els Pardon

    (Structural Biology Research Center, VIB, Vrije Universiteit Brussel (VUB))

  • Jan Steyaert

    (Structural Biology Brussels, Vrije Universiteit Brussel (VUB))

  • Brian K. Kobilka

    (Stanford University)

  • Roger K. Sunahara

    (University of Michigan Medical School
    University of California San Diego School of Medicine)

Abstract

Here, pharmacological and biochemical evidence is provided that shows that G-protein coupling to the β2-adrenergic receptor stabilizes a ‘closed’ conformation of the G-protein-coupled receptor (GPCR) and that that the effects of the G protein on the ligand-binding site of the GPCR are observed even in the absence of a bound agonist.

Suggested Citation

  • Brian T. DeVree & Jacob P. Mahoney & Gisselle A. Vélez-Ruiz & Soren G. F. Rasmussen & Adam J. Kuszak & Elin Edwald & Juan-Jose Fung & Aashish Manglik & Matthieu Masureel & Yang Du & Rachel A. Matt & E, 2016. "Allosteric coupling from G protein to the agonist-binding pocket in GPCRs," Nature, Nature, vol. 535(7610), pages 182-186, July.
    • Handle: RePEc:nat:nature:v:535:y:2016:i:7610:d:10.1038_nature18324
    DOI: 10.1038/nature18324
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    Citations

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    Cited by:

    1. Xinyu Xu & Jeremy Shonberg & Jonas Kaindl & Mary J. Clark & Anne Stößel & Luis Maul & Daniel Mayer & Harald Hübner & Kunio Hirata & A. J. Venkatakrishnan & Ron O. Dror & Brian K. Kobilka & Roger K. Su, 2023. "Constrained catecholamines gain β2AR selectivity through allosteric effects on pocket dynamics," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. 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.
    3. 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.
    4. Kazem Asadollahi & Sunnia Rajput & Lazarus Andrew Zhang & Ching-Seng Ang & Shuai Nie & Nicholas A. Williamson & Michael D. W. Griffin & Ross A. D. Bathgate & Daniel J. Scott & Thomas R. Weikl & Guy N., 2023. "Unravelling the mechanism of neurotensin recognition by neurotensin receptor 1," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    5. Kelly J. Culhane & Tejas M. Gupte & Indrani Madhugiri & Chetan J. Gadgil & Sivaraj Sivaramakrishnan, 2022. "Kinetic model of GPCR-G protein interactions reveals allokairic modulation of signaling," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    6. Jun Xu & Qinggong Wang & Harald Hübner & Yunfei Hu & Xiaogang Niu & Haoqing Wang & Shoji Maeda & Asuka Inoue & Yuyong Tao & Peter Gmeiner & Yang Du & Changwen Jin & Brian K. Kobilka, 2023. "Structural and dynamic insights into supra-physiological activation and allosteric modulation of a muscarinic acetylcholine receptor," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    7. Anastasiia Gusach & Yang Lee & Armin Nikpour Khoshgrudi & Elizaveta Mukhaleva & Ning Ma & Eline J. Koers & Qingchao Chen & Patricia C. Edwards & Fanglu Huang & Jonathan Kim & Filippo Mancia & Dmitry B, 2024. "Molecular recognition of an odorant by the murine trace amine-associated receptor TAAR7f," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    8. Christoph Klenk & Maria Scrivens & Anina Niederer & Shuying Shi & Loretta Mueller & Elaine Gersz & Maurice Zauderer & Ernest S. Smith & Ralf Strohner & Andreas Plückthun, 2023. "A Vaccinia-based system for directed evolution of GPCRs in mammalian cells," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    9. Minfei Su & Navid Paknejad & Lan Zhu & Jinan Wang & Hung Nguyen Do & Yinglong Miao & Wei Liu & Richard K. Hite & Xin-Yun Huang, 2022. "Structures of β1-adrenergic receptor in complex with Gs and ligands of different efficacies," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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