Receptor pharmacology articles within Nature

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• Article | 08 May 2024

  Structural pharmacology and therapeutic potential of 5-methoxytryptamines

  Detailed analyses of the serotonin receptor 5-HT_1A and the psychedelic 5-methoxy-N,N-dimethyltryptamine reveal the differences in receptor structural pharmacology that mediate signalling specificity, efficacy and potency, findings that may facilitate the development of new neuropsychiatric therapeutics.

  • Audrey L. Warren
  • , David Lankri
  •  & Daniel Wacker

• Article | 10 April 2024

  Bitter taste receptor activation by cholesterol and an intracellular tastant

  Cryo-electron microscopy structures of the type 2 taste receptor TAS2R14 in complex with Ggust and Gi1 identify cholesterol as an orthosteric agonist and the bitter tastant cmpd28.1 as a positive allosteric modulator and agonist.

  • Yoojoong Kim
  • , Ryan H. Gumpper
  •  & Bryan L. Roth

• Article
  07 June 2023 | Open Access

  Class B1 GPCR activation by an intracellular agonist

  A new intracellular agonist-binding pocket is identified that is common to many G protein-coupled receptors, which will have implications for the development of biased compounds that target this large group of receptors.

  • Kazuhiro Kobayashi
  • , Kouki Kawakami
  •  & Osamu Nureki

• Article | 15 March 2023

  Structural basis of odorant recognition by a human odorant receptor

  Through the use of cryo-electron microscopy and molecular dynamics stimulations, mechanistic insight into the binding of an odorant to the human odorant receptor OR51E2 is provided.

  • Christian B. Billesbølle
  • , Claire A. de March
  •  & Aashish Manglik

• Article | 08 March 2023

  Molecular sensing of mechano- and ligand-dependent adhesion GPCR dissociation

  A technique to detect the release of N-terminal fragments of Drosophila adhesion G-protein-coupled receptors (aGPCRs) provides insight into the dissociation of aGPCRs, and shows that receptor autoproteolysis enables non-cell-autonomous activity of aGPCRs in the brain.

  • Nicole Scholz
  • , Anne-Kristin Dahse
  •  & Tobias Langenhan

• Article | 08 August 2022

  Autoantibody mimicry of hormone action at the thyrotropin receptor

  Cryo-electron microscopy structures of the thyrotropin receptor reveal the basis for the activation of the receptor by autoantibodies in patients with Graves’ disease.

  • Bryan Faust
  • , Christian B. Billesbølle
  •  & Aashish Manglik

• Article | 08 December 2021

  Structures of the σ₂ receptor enable docking for bioactive ligand discovery

  Crystal structures of the σ₂ receptor are determined and used to perform a docking screen of nearly 500 million molecules, identifying σ₂-selective ligands and providing insight into the role of σ₂ in neuropathic pain.

  • Assaf Alon
  • , Jiankun Lyu
  •  & Andrew C. Kruse

• Article | 08 December 2021

  Structural basis of inhibition of the human SGLT2–MAP17 glucose transporter

  Using cryogenic electron microscopy, the structure of the human SGLT2–MAP17 complex captured in the empagliflozin-bound state reveals the inhibitory mechanism of these anti-diabetic drugs.

  • Yange Niu
  • , Rui Liu
  •  & Lei Chen

• Article | 17 November 2021

  Structure, function and pharmacology of human itch receptor complexes

  Cryo-electron microscopy structures of the MRGPRX2–G_i1 trimer in complex with polycationic compound 48/80 or inflammatory peptides provide insights into the sensing of cationic allergens by MRGPRX2, potentially facilitating the design of therapies to prevent unwanted pseudoallergic reactions.

  • Fan Yang
  • , Lulu Guo
  •  & Jin-Peng Sun

• Article | 08 September 2021

  Positive allosteric mechanisms of adenosine A₁ receptor-mediated analgesia

  MIPS521, a positive allosteric modulator of the adenosine A₁ receptor, has analgesic properties in a rat model of neuropathic pain through a mechanism by which MIPS521 stabilizes the complex between adenosine, receptor and G protein.

  • Christopher J. Draper-Joyce
  • , Rebecca Bhola
  •  & Arthur Christopoulos

• Article | 24 March 2021

  Structural insights into the lipid and ligand regulation of serotonin receptors

  Cryo-electron microscopy structures of three different serotonin receptors in complex with serotonin and other agonists provide insights into the role of lipids in regulating these receptors and the structural basis of ligand recognition.

  • Peiyu Xu
  • , Sijie Huang
  •  & H. Eric Xu

• Article | 22 July 2020

  Structural basis of GPBAR activation and bile acid recognition

  Using cryo-electron microscopy, the authors report the structures of G-protein-coupled bile acid receptor–G_s complexes and reveal the structural basis of bile acid recognition.

  • Fan Yang
  • , Chunyou Mao
  •  & Yan Zhang

• Article | 10 February 2020

  Virtual discovery of melatonin receptor ligands to modulate circadian rhythms

  A computational screen of an ultra-large virtual library against the structure of the melatonin receptor found nanomolar ligands, and ultimately two selective MT₁ inverse agonists that induced phase advancement of the mouse circadian clock when given at subjective dusk.

  • Reed M. Stein
  • , Hye Jin Kang
  •  & Margarita L. Dubocovich

• Article | 16 January 2020

  Structure of the neurotensin receptor 1 in complex with β-arrestin 1

  A cryo-electron microscopy structure of the neurotensin receptor 1 in complex with β-arrestin 1 is reported.

  • Weijiao Huang
  • , Matthieu Masureel
  •  & Brian K. Kobilka

• Article | 08 January 2020

  Activation of the GLP-1 receptor by a non-peptidic agonist

  The structure of GLP-1R and its G protein in complex with the small molecule TT-OAD2 sheds light on how the TT-OAD2 agonist can activate the receptor and provides insights into the development of therapeutic agents for metabolic disorders.

  • Peishen Zhao
  • , Yi-Lynn Liang
  •  & Denise Wootten

• Article | 02 January 2019

  GABA_A receptor signalling mechanisms revealed by structural pharmacology

  Cryo-electron microscopy structures are reported in which the full-length human α1β3γ2L GABA_A receptor in lipid nanodiscs is bound to the channel-blocker picrotoxin, the competitive antagonist bicuculline, the agonist GABA, and the benzodiazepines alprazolam and diazepam.

  • Simonas Masiulis
  • , Rooma Desai
  •  & A. Radu Aricescu

• Article | 12 September 2018

  Optimized arylomycins are a new class of Gram-negative antibiotics

  Chemical optimization of arylomycins results in an inhibitor of bacterial type I signal peptidase that shows activity both against multidrug-resistant clinical isolates of Gram-negative bacteria in vitro and in several in vivo infection models.

  • Peter A. Smith
  • , Michael F. T. Koehler
  •  & Christopher E. Heise

• Review Article | 04 July 2018

  Structural insights into G-protein-coupled receptor allostery

  High-resolution structural studies of GPCRs have led to insights into the role of allostery in GPCR-mediated signal transduction.

  • David M. Thal
  • , Alisa Glukhova
  •  & Arthur Christopoulos

• Article | 20 June 2018

  Structure of the adenosine-bound human adenosine A₁ receptor–G_i complex

  The cryo-electron microscopy structure of the human adenosine A₁ receptor in complex with adenosine and heterotrimeric G_i2 protein provides molecular insights into receptor and G-protein selectivity.

  • Christopher J. Draper-Joyce
  • , Maryam Khoshouei
  •  & Arthur Christopoulos

• Article | 13 June 2018

  Structure of the µ-opioid receptor–G_i protein complex

  A cryo-electron structure of the µ-opioid receptor in complex with the peptide agonist DAMGO and the inhibitory G protein G_i reveals structural determinants of its G protein-binding specificity.

  • Antoine Koehl
  • , Hongli Hu
  •  & Brian K. Kobilka

• Letter | 24 January 2018

  Structure of the D2 dopamine receptor bound to the atypical antipsychotic drug risperidone

  An X-ray structure of the D2 dopamine receptor bound to the atypical antipsychotic drug risperidone reveals an extended binding pocket and indicates structural features that could be used to design drugs that specifically target the D2 receptor.

  • Sheng Wang
  • , Tao Che
  •  & Bryan L. Roth

• Article | 31 May 2017

  Crystal structure of the GLP-1 receptor bound to a peptide agonist

  The solved crystal structure of the GLP-1 receptor bound to a truncated agonist enables the design of synthetic agonists that exhibit potent activity in vivo.

  • Ali Jazayeri
  • , Mathieu Rappas
  •  & Fiona H. Marshall

• Letter | 26 April 2017

  Structural insight into allosteric modulation of protease-activated receptor 2

  Crystal structures of protease-activated receptor 2 (PAR2) in complex with two different antagonist ligands and with a blocking antibody reveal binding sites that are distinct from those found on PAR1, offering new leads for structure-based drug design.

  • Robert K. Y. Cheng
  • , Cédric Fiez-Vandal
  •  & Niek Dekker

• Article | 24 April 2017

  Phase-plate cryo-EM structure of a class B GPCR–G-protein complex

  Volta phase-plate cryo-electron microscopy reveals the structure of the full-length calcitonin receptor in complex with its peptide ligand and Gα_sβγ.

  • Yi-Lynn Liang
  • , Maryam Khoshouei
  •  & Patrick M. Sexton

• Letter | 07 December 2016

  Structure of CC chemokine receptor 2 with orthosteric and allosteric antagonists

  The crystal structure of CCR2 chemokine receptor in a complex with two different antagonists—one orthosteric the other allosteric—which functionally cooperate to inhibit CCR2.

  • Yi Zheng
  • , Ling Qin
  •  & Tracy M. Handel

• Review Article | 01 December 2016

  Organization and functions of mGlu and GABA_B receptor complexes

  This Review discusses current knowledge of the structure, function and interactions of the metabotropic glutamate and GABA_B receptors and the potential to target receptor subunits for future therapeutic intervention in neurological and mental health disorders.

  • Jean-Philippe Pin
  •  & Bernhard Bettler

• Letter | 16 November 2016

  High-resolution crystal structure of the human CB1 cannabinoid receptor

  The authors report a 2.6 Å resolution crystal structure of the human CB1 cannabinoid receptor trapped in the inactive conformation and bound to the antagonist taranabant.

  • Zhenhua Shao
  • , Jie Yin
  •  & Daniel M. Rosenbaum

• Letter | 13 July 2016

  Allosteric nanobodies reveal the dynamic range and diverse mechanisms of G-protein-coupled receptor activation

  Stabilization of an active and inactive conformation of the β₂-adrenergic receptor by allosteric nanobodies reveals differential ligand-dependent regulation of receptor states to control G-protein-coupled receptor activation.

  • Dean P. Staus
  • , Ryan T. Strachan
  •  & Robert J. Lefkowitz

• News & Views | 16 May 2012

  How opioid drugs bind to receptors

  The search for safe, non-addictive versions of morphine and other opioid drugs has just received a boost with the solving of the crystal structures of the receptors to which the drugs bind. See Articles p.321 & p.327, Letters p.395 & p.400

  • Marta Filizola
  •  & Lakshmi A. Devi

• Letter | 16 May 2012

  Structure of the δ-opioid receptor bound to naltrindole

  The X-ray crystal structure of the mouse δ-opioid receptor in complex with the subtype-selective antagonist naltrindole is reported.

  • Sébastien Granier
  • , Aashish Manglik
  •  & Brian K. Kobilka

• News & Views | 22 February 2012

  Muscarinic receptors become crystal clear

  Muscarinic acetylcholine receptors mediate many physiological responses of the nervous system. Structures of two of these receptors yield insight into how they bind drugs and their mechanism of action. See Letters p.547 & 552

  • Rebecca L. Kow
  •  & Neil M. Nathanson

• Letter | 04 September 2011

  Antidiabetic actions of a non-agonist PPARγ ligand blocking Cdk5-mediated phosphorylation

  • Jang Hyun Choi
  • , Alexander S. Banks
  •  & Patrick R. Griffin

• Research Highlights | 27 July 2011

  Target for blocking cocaine

• Letter | 27 July 2011

  Oxysterols direct B-cell migration through EBI2

  • Changlu Liu
  • , Xia V. Yang
  •  & Timothy W. Lovenberg

• Article | 22 June 2011

  Structure of the human histamine H₁ receptor complex with doxepin

  • Tatsuro Shimamura
  • , Mitsunori Shiroishi
  •  & So Iwata

• Letter | 15 June 2011

  NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses

  • Anita E. Autry
  • , Megumi Adachi
  •  & Lisa M. Monteggia

• Letter | 18 May 2011

  Agonist-bound adenosine A_2A receptor structures reveal common features of GPCR activation

  • Guillaume Lebon
  • , Tony Warne
  •  & Christopher G. Tate

• Letter | 12 January 2011

  The structural basis for agonist and partial agonist action on a β₁-adrenergic receptor

  Here, the X-ray crystal structure of the β₁ adrenergic receptor, a G-protein-coupled receptor, bound to four small molecules that either act as full agonists or partial agonists is solved. The structures show that agonist binding induces a contraction of the catecholamine-binding pocket relative to the antagonist-bound receptor. This work reveals the pharmacological differences between different ligand classes, which should facilitate the structure-based design of new drugs with predictable efficacies.

  • Tony Warne
  • , Rouslan Moukhametzianov
  •  & Christopher G. Tate

• Research Highlights | 24 November 2010

  Structural biology: Dopamine receptor revealed

• News & Views | 10 February 2010

  Lack of inhibition leads to abuse

  Chronic drug use can lead to addiction, which is initiated by specific brain circuits. The mystery of how one class of drugs, the benzodiazepines, affects activity in this circuitry has finally been solved.

  • Arthur C. Riegel
  •  & Peter W. Kalivas