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Rearrangement of the transmembrane domain interfaces associated with the activation of a GPCR hetero-oligomer

Author

Listed:
  • Li Xue

    (Huazhong University of Science and Technology)

  • Qian Sun

    (Huazhong University of Science and Technology)

  • Han Zhao

    (Huazhong University of Science and Technology)

  • Xavier Rovira

    (Université de Montpellier
    University of Vic - Central University of Catalonia, C. de la Laura, 13)

  • Siyu Gai

    (Huazhong University of Science and Technology)

  • Qianwen He

    (Huazhong University of Science and Technology)

  • Jean-Philippe Pin

    (Université de Montpellier)

  • Jianfeng Liu

    (Huazhong University of Science and Technology)

  • Philippe Rondard

    (Université de Montpellier)

Abstract

G protein-coupled receptors (GPCRs) can integrate extracellular signals via allosteric interactions within dimers and higher-order oligomers. However, the structural bases of these interactions remain unclear. Here, we use the GABAB receptor heterodimer as a model as it forms large complexes in the brain. It is subjected to genetic mutations mainly affecting transmembrane 6 (TM6) and involved in human diseases. By cross-linking, we identify the transmembrane interfaces involved in GABAB1-GABAB2, as well as GABAB1-GABAB1 interactions. Our data are consistent with an oligomer made of a row of GABAB1. We bring evidence that agonist activation induces a concerted rearrangement of the various interfaces. While the GB1-GB2 interface is proposed to involve TM5 in the inactive state, cross-linking of TM6s lead to constitutive activity. These data bring insight for our understanding of the allosteric interaction between GPCRs within oligomers.

Suggested Citation

  • Li Xue & Qian Sun & Han Zhao & Xavier Rovira & Siyu Gai & Qianwen He & Jean-Philippe Pin & Jianfeng Liu & Philippe Rondard, 2019. "Rearrangement of the transmembrane domain interfaces associated with the activation of a GPCR hetero-oligomer," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10834-5
    DOI: 10.1038/s41467-019-10834-5
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    Cited by:

    1. Panpan Zhang & Masahiro Maruoka & Ryo Suzuki & Hikaru Katani & Yu Dou & Daniel M. Packwood & Hidetaka Kosako & Motomu Tanaka & Jun Suzuki, 2023. "Extracellular calcium functions as a molecular glue for transmembrane helices to activate the scramblase Xkr4," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Junke Liu & Hengmin Tang & Chanjuan Xu & Shengnan Zhou & Xunying Zhu & Yuanyuan Li & Laurent Prézeau & Tao Xu & Jean-Philippe Pin & Philippe Rondard & Wei Ji & Jianfeng Liu, 2022. "Biased signaling due to oligomerization of the G protein-coupled platelet-activating factor receptor," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Marie-Lise Jobin & Sana Siddig & Zsombor Koszegi & Yann Lanoiselée & Vladimir Khayenko & Titiwat Sungkaworn & Christian Werner & Kerstin Seier & Christin Misigaiski & Giovanna Mantovani & Markus Sauer, 2023. "Filamin A organizes γ‑aminobutyric acid type B receptors at the plasma membrane," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Sayaka Oda & Kazuhiro Nishiyama & Yuka Furumoto & Yohei Yamaguchi & Akiyuki Nishimura & Xiaokang Tang & Yuri Kato & Takuro Numaga-Tomita & Toshiyuki Kaneko & Supachoke Mangmool & Takuya Kuroda & Reish, 2022. "Myocardial TRPC6-mediated Zn2+ influx induces beneficial positive inotropy through β-adrenoceptors," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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