G protein-coupled receptors articles within Nature

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  • Article |

    Time-resolved cryo-EM is used to capture structural transitions during G-protein activation stimulated by a G-protein-coupled receptor.

    • Makaía M. Papasergi-Scott
    • , Guillermo Pérez-Hernández
    •  & Georgios Skiniotis

  • Article
    | Open Access

    Latrophilin-3 organizes synapses through a convergent dual-pathway mechanism in which Gαs signalling is activated and phase-separated postsynaptic protein scaffolds are recruited.

    • Shuai Wang
    • , Chelsea DeLeon
    •  & Thomas C. Südhof

  • Article
    | Open Access

    Structures of the glucagon receptor bound to β-arrestin 1 are reported, providing further information about the arrestin-mediated modulation of G protein-coupled receptors.

    • Kun Chen
    • , Chenhui Zhang
    •  & Beili Wu

  • Article
    | Open Access

    Cryo-electron microscopy structures of ligand-free, agonist-bound and antagonist-bound Ste2 show that this class D1 G protein-coupled receptor has a distinct mechanism of activation compared with other receptor classes.

    • Vaithish Velazhahan
    • , Ning Ma
    •  & Christopher G. Tate

  • Article |

    Cryo-electron microscopy structures show that metabotropic glutamate receptor 2 forms a dimer to which only one G protein is coupled, revealing the basis for asymmetric signal transduction.

    • Alpay B. Seven
    • , Ximena Barros-Álvarez
    •  & Georgios Skiniotis

  • Article |

    Cryo-EM structures of human calcium-sensing receptor reveal intrinsic asymmetry in the receptor homodimer upon activation that is stabilized by calcimimetic drugs adopting distinct poses in the two protomers, priming one protomer for G-protein coupling.

    • Yang Gao
    • , Michael J. Robertson
    •  & Georgios Skiniotis

  • Article |

    Cryo-electron microscopy structures of homo- and heterodimers of mGlu2 and mGlu7 provide insights into their dimerization modes and the subunit conformational changes that characterize the activation of these class C G-protein-coupled receptors.

    • Juan Du
    • , Dejian Wang
    •  & Qiang Zhao

  • Article
    | Open Access

    Cryo-electron microscopy structure of heterodimeric GABAB receptor in complex with Gi1 protein reveals that the mode of G-protein binding in this class-C G-protein-coupled receptor differs from that of other classes.

    • Cangsong Shen
    • , Chunyou Mao
    •  & Jianfeng Liu

  • Article |

    The structure of the GABAB receptor in an inactive state reveals, amongst other features, a latch between the two subunits that locks the transmembrane domain interface, and the presence of large phospholipids that may modulate receptor function.

    • Jinseo Park
    • , Ziao Fu
    •  & Qing R. Fan

  • Article |

    Cryo-electron microscopy structures of heterodimeric and homodimeric full-length GABAB receptors, combined with cellular signalling assays, shed light on the mechanisms that underpin signal transduction mediated by these receptors.

    • Makaía M. Papasergi-Scott
    • , Michael J. Robertson
    •  & Georgios Skiniotis

  • Article |

    Cryo-electron microscopy structures of apo, agonist- and positive allosteric modulator-bound forms of the GB1–GB2 heterodimer of the metabotropic γ-aminobutyric acid (GABA) receptor shed light on the activation mechanism of this receptor.

    • Hamidreza Shaye
    • , Andrii Ishchenko
    •  & Vadim Cherezov

  • Article |

    A cryo-electron microscopy structure of the β1-adrenoceptor coupled to β-arrestin 1 and activated by the biased agonist formoterol, as well as the crystal structure of a related formoterol-bound adrenoreceptor, provide insights into biased signalling in these systems.

    • Yang Lee
    • , Tony Warne
    •  & Christopher G. Tate

  • Article |

    High-resolution crystal structures of the rat succinate receptor SUCNR1 in an inactive confirmation, and the humanized rat SUCNR1 bound to an antagonist, provide insights into the structure of these receptors and the species selectivity of antagonist binding.

    • Matthias Haffke
    • , Dominique Fehlmann
    •  & Veli-Pekka Jaakola

  • Article |

    Cryo-electron microscopy structures of human neurotensin receptor 1 in complex with Gi1 protein and the agonist JMV449 reveal a non-canonical state that may represent an intermediate form in G-protein activation.

    • Hideaki E. Kato
    • , Yan Zhang
    •  & Georgios Skiniotis

  • Letter |

    The high-resolution structure of the serotonin 5-HT1B receptor in complex with the agonist donitriptan and a Go heterotrimer highlights features that may underlie the specificity of receptor–G-protein coupling and kinetics of signalling.

    • Javier García-Nafría
    • , Rony Nehmé
    •  & Christopher G. Tate

  • Article |

    Computational docking to the the μ-opioid-receptor identifies PZM21, a novel selective biased agonist that generates substantial affective analgesia in mice without altering respiration or inducing drug reinforcement.

    • Aashish Manglik
    • , Henry Lin
    •  & Brian K. Shoichet

  • Letter |

    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.

    • Brian T. DeVree
    • , Jacob P. Mahoney
    •  & Roger K. Sunahara

  • Letter |

    The X-ray crystal structure of the transmembrane portion of the human glucagon receptor, a class B G-protein-coupled receptor (GPCR), is solved in the presence of the antagonist MK-0893, with potential implications for the development of therapeutics that target other class B GPCRs.

    • Ali Jazayeri
    • , Andrew S. Doré
    •  & Fiona H. Marshall

  • Letter |

    A series of intramolecular fluorescent FlAsH BRET reporters is used to monitor conformational changes in β-arrestin2 following activation of seven G-protein-coupled receptors (GPCRs), showing that different GPCRs produce distinct β-arrestin2 conformational signatures that correlate with the stability of the receptor–arrestin complex and the role of β-arrestin2 in activating or dampening downstream signalling events, which explains how different GPCRs can use a common effector for different purposes.

    • Mi-Hye Lee
    • , Kathryn M. Appleton
    •  & Louis M. Luttrell

  • Letter |

    A series of FRET-based β-arrestin2 biosensors are used to study the dynamics and conformational changes that occur when β-arrestin2 binds to and dissociates from the β2-adrenergic receptor in living cells; results show that after β-arrestin2 dissociates from the β2-adrenergic receptor, it stays at the cell membrane in an active conformation for a while, indicating that β-arrestin is able to signal in a G-protein-coupled receptor (GPCR)-free state.

    • Susanne Nuber
    • , Ulrike Zabel
    •  & Carsten Hoffmann

  • Article |

    X-ray crystal structures of the M1 and M4 muscarinic acetylcholine receptors, revealing differences in the orthosteric and allosteric binding sites that help to explain the subtype selectivity of drugs targeting this family of receptors.

    • David M. Thal
    • , Bingfa Sun
    •  & Arthur Christopoulos

  • Article |

    Yeast-based screening identifies the benzodiazepine drug lorazepam as a non-selective positive allosteric modulator of the G-protein-coupled receptor (GPCR) GPR68; homology modelling and molecular docking of 3.1 million molecules found a new compound, ‘ogerin’, as a potent GPR68 modulator, which suppressed recall in fear conditioning in wild-type mice, and the general method of combining physical and structure-based screening may lead to the discovery of selective ligands for other GPCRs.

    • Xi-Ping Huang
    • , Joel Karpiak
    •  & Bryan L. Roth

  • Letter |

    smFRET is used to probe the activation mechanism of two full-length mammalian glutamate receptors, revealing that the extracellular ligand-binding domains of these G-protein-coupled receptors interconvert between three confirmations (resting, activated and a short-lived intermediate state), and that the efficacy of an orthosteric agonist correlates with the degree of occupancy of the active state.

    • Reza Vafabakhsh
    • , Joshua Levitz
    •  & Ehud Y. Isacoff

  • Article |

    X-ray crystallography and molecular dynamics simulations of the μ-opioid receptor reveal the conformational changes in the extracellular and intracellular domains of this G-protein-coupled receptor that are associated with its activation.

    • Weijiao Huang
    • , Aashish Manglik
    •  & Brian K. Kobilka

  • Letter |

    NMR spectroscopy reveals the conformational changes of the μ-opioid receptor that are associated with receptor activation, helping to explain why the allosteric coupling between the agonist-binding pocket and the cytoplasmic G-protein-coupling interface of this receptor is relatively weak.

    • Rémy Sounier
    • , Camille Mas
    •  & Sébastien Granier

  • Article |

    G protein-coupled receptors are a large family of signalling proteins that mediate cellular responses primarily via G proteins or arrestins, and they are targets of one-third of the current clinically used drugs; here, an active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin-1 is determined, revealing unique structural features that may constitute essential elements for arrestin-biased signalling.

    • Yanyong Kang
    • , X. Edward Zhou
    •  & H. Eric Xu

  • Analysis |

    There are ∼800 human GPCRs and 16 different Gα proteins; this study revealed the molecular details of Gα activation by GPCRs and suggests that a universal activation mechanism governs Gα activation—the details of this mechanism can explain how the GPCR–Gα system diversified rapidly, while conserving the allosteric activation mechanism.

    • Tilman Flock
    • , Charles N. J. Ravarani
    •  & M. Madan Babu

  • Article |

    Two X-ray crystal structures are presented of the human P2Y1 G-protein-coupled receptor, which is an important target for anti-thrombotic drugs; the structures unexpectedly reveal two ligand-binding sites.

    • Dandan Zhang
    • , Zhan-Guo Gao
    •  & Beili Wu

  • Article |

    An X-ray structure is presented for metabotropic glutamate receptor 5, a class C G-protein-coupled glutamate receptor linked to fragile X syndrome and neurological disorders; this study provides insights into the protein’s mechanism of action.

    • Andrew S. Doré
    • , Krzysztof Okrasa
    •  & Fiona H. Marshall

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