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Structural insights into G-protein-coupled receptor allostery

Author

Listed:
  • David M. Thal

    (Monash University)

  • Alisa Glukhova

    (Monash University)

  • Patrick M. Sexton

    (Monash University)

  • Arthur Christopoulos

    (Monash University)

Abstract

G-protein-coupled receptors (GPCRs) are key cell-surface proteins that transduce external environmental cues into biochemical signals across the membrane. GPCRs are intrinsically allosteric proteins; they interact via spatially distinct yet conformationally linked domains with both endogenous and exogenous proteins, nutrients, metabolites, hormones, small molecules and biological agents. Here we explore recent high-resolution structural studies, which are beginning to unravel the atomic details of allosteric transitions that govern GPCR biology, as well as highlighting how the wide diversity of druggable allosteric sites across these receptors present opportunities for developing new classes of therapeutics.

Suggested Citation

  • David M. Thal & Alisa Glukhova & Patrick M. Sexton & Arthur Christopoulos, 2018. "Structural insights into G-protein-coupled receptor allostery," Nature, Nature, vol. 559(7712), pages 45-53, July.
    • Handle: RePEc:nat:nature:v:559:y:2018:i:7712:d:10.1038_s41586-018-0259-z
    DOI: 10.1038/s41586-018-0259-z
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    Cited by:

    1. Geng Chen & Jun Xu & Asuka Inoue & Maximilian F. Schmidt & Chen Bai & Qiuyuan Lu & Peter Gmeiner & Zheng Liu & Yang Du, 2022. "Activation and allosteric regulation of the orphan GPR88-Gi1 signaling complex," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Yosuke Toyoda & Angqi Zhu & Fang Kong & Sisi Shan & Jiawei Zhao & Nan Wang & Xiaoou Sun & Linqi Zhang & Chuangye Yan & Brian K. Kobilka & Xiangyu Liu, 2023. "Structural basis of α1A-adrenergic receptor activation and recognition by an extracellular nanobody," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Jie Heng & Yunfei Hu & Guillermo Pérez-Hernández & Asuka Inoue & Jiawei Zhao & Xiuyan Ma & Xiaoou Sun & Kouki Kawakami & Tatsuya Ikuta & Jienv Ding & Yujie Yang & Lujia Zhang & Sijia Peng & Xiaogang N, 2023. "Function and dynamics of the intrinsically disordered carboxyl terminus of β2 adrenergic receptor," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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