4.8 Article

Molecular mechanism of biased signaling at the kappa opioid receptor

相关参考文献

注意:仅列出部分参考文献,下载原文获取全部文献信息。
Article Biochemistry & Molecular Biology

Insights into distinct signaling profiles of the μOR activated by diverse agonists

Qianhui Qu et al.

Summary: This study investigated the mechanistic basis of action of two mu-opioid receptor (mu OR) agonists, LFT and MP, with different safety profiles, and found that they exhibited markedly different efficacy profiles for G protein subtype activation and beta-arrestin recruitment.

NATURE CHEMICAL BIOLOGY (2023)

Review Biochemistry & Molecular Biology

Structural basis of GPCR coupling to distinct signal transducers: implications for biased signaling

Mohammad Seyedabad et al.

Summary: The structures of GPCRs bound to their interaction partners do not reveal a clear conformational basis for signaling bias, suggesting that there may be no generalizable GPCR conformations conducive to binding a particular type of partner, or the subtle differences in residue orientation and interactions may determine partner preference, or the dynamics of GPCR binding to different types of partners rather than the structures of the final complexes might underlie transducer bias.

TRENDS IN BIOCHEMICAL SCIENCES (2022)

Article Neurosciences

Signaling snapshots of a serotonin receptor activated by the prototypical psychedelic LSD

Can Cao et al.

Summary: This study determines the binding of LSD to HTR2B receptors in different states using cryo-EM structures, providing molecular insights into the mechanism of LSD's psychedelic effects and accelerating the discovery of novel psychedelic drugs.

NEURON (2022)

Article Immunology

Nalfurafine reduces neuroinflammation and drives remyelination in models of CNS demyelinating disease

Lisa Denny et al.

Summary: Nalfurafine shows potential in promoting recovery and remyelination in multiple sclerosis (MS), mediating recovery in EAE in a KOR-dependent fashion, reducing CNS infiltration, especially CD4(+) and CD8(+) T cells, and promoting a more immunoregulatory environment, while also promoting remyelination in the absence of peripheral immune cell invasion in the cuprizone demyelination model.

CLINICAL & TRANSLATIONAL IMMUNOLOGY (2021)

Article Biology

Controlling opioid receptor functional selectivity by targeting distinct subpockets of the orthosteric site

Rajendra Uprety et al.

Summary: This study utilized crystal structures of opioid receptors to design novel MOR and KOR agonists with reduced arrestin signaling, which showed efficient analgesic effects with attenuated liabilities. The findings validate a novel structure-inspired paradigm for achieving beneficial in vivo profiles for analgesia through different mechanisms including bias, partial agonism, and dual MOR/KOR agonism.
Review Biochemistry & Molecular Biology

Structural Insights Accelerate the Discovery of Opioid Alternatives

Tao Che et al.

Summary: Opioids like morphine and oxycodone are commonly used for pain relief, but they come with high abuse potential and fatal side effects. Efforts to find safer nonopioid analgesics targeting the mu-opioid receptor are facing challenges, but advancements in understanding receptor activation and signaling are leading to the discovery of alternative strategies and targets.

ANNUAL REVIEW OF BIOCHEMISTRY, VOL 90, 2021 (2021)

Review Biochemistry & Molecular Biology

Biased ligands at opioid receptors: Current status and future directions

Tao Che et al.

Summary: The opioid crisis has led to a search for safer and more effective opioids. The discovery of biased opioid ligands offers a potential alternative, but questions remain about their therapeutic benefits. More research is needed in this important area to understand the implications of biased agonism.

SCIENCE SIGNALING (2021)

Article Chemistry, Medicinal

Delineating the Ligand-Receptor Interactions That Lead to Biased Signaling at the μ-Opioid Receptor

Brendan Kelly et al.

Summary: Biased agonists selectively stimulate certain signaling pathways controlled by GPCRs to maximize efficacy and minimize side effects. Designing biased agonists for the mu OR remains challenging due to unclear ligand-mediated interactions and differences in interaction with the binding pocket may lead to distinct bias profiles.

JOURNAL OF CHEMICAL INFORMATION AND MODELING (2021)

Article Biochemistry & Molecular Biology

Molecular insights into the biased signaling mechanism of the μ-opioid receptor

Xiaojing Cong et al.

Summary: GPCR functional selectivity presents new opportunities for designing safer drugs. Through a combination of functional assays, solution NMR spectroscopy, and molecular dynamic simulations, our study has identified specific mu OR conformations induced by G protein-biased agonists, shedding light on the dynamic mechanism enabling opioid ligands to preferentially activate the G protein pathway.

MOLECULAR CELL (2021)

Article Multidisciplinary Sciences

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

Weijiao Huang et al.

NATURE (2020)

Article Multidisciplinary Sciences

Structure of the M2 muscarinic receptor-β-arrestin complex in a lipid nanodisc

Dean P. Staus et al.

NATURE (2020)

Article Multidisciplinary Sciences

The atomistic level structure for the activated human.-opioid receptor bound to the full Gi protein and the MP1104 agonist

Amirhossein Mafi et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

Article Multidisciplinary Sciences

Molecular mechanism of biased signaling in a prototypical G protein-coupled receptor

Carl-Mikael Suomivuori et al.

SCIENCE (2020)

Article Multidisciplinary Sciences

Nanobody-enabled monitoring of kappa opioid receptor states

Tao Che et al.

NATURE COMMUNICATIONS (2020)

Article Biochemistry & Molecular Biology

Low intrinsic efficacy for G protein activation can explain the improved side effect profiles of new opioid agonists

Alexander Gillis et al.

SCIENCE SIGNALING (2020)

Article Biochemistry & Molecular Biology

TRUPATH, an open-source biosensor platform for interrogating the GPCR transducerome

Reid H. J. Olsen et al.

NATURE CHEMICAL BIOLOGY (2020)

Article Biochemistry & Molecular Biology

Illuminating G-Protein-Coupling Selectivity of GPCRs

Asuka Inoue et al.

Article Multidisciplinary Sciences

Elucidating the active δ-opioid receptor crystal structure with peptide and small-molecule agonists

Tobias Claff et al.

SCIENCE ADVANCES (2019)

Article Biochemistry & Molecular Biology

Angiotensin Analogs with Divergent Bias Stabilize Distinct Receptor Conformations

Laura M. Wingler et al.

Article Biochemistry & Molecular Biology

Structure of the Nanobody-Stabilized Active State of the Kappa Opioid Receptor

Tao Che et al.

Article Multidisciplinary Sciences

Catalytic activation of β-arrestin by GPCRs

Kelsie Eichel et al.

NATURE (2018)

Article Multidisciplinary Sciences

Molecular mechanism of GPCR-mediated arrestin activation

Naomi R. Latorraca et al.

NATURE (2018)

Review Biotechnology & Applied Microbiology

Biased signalling: from simple switches to allosteric microprocessors

Jeffrey S. Smith et al.

NATURE REVIEWS DRUG DISCOVERY (2018)

Article Chemistry, Medicinal

GPU-Accelerated Molecular Dynamics and Free Energy Methods in Amber18: Performance Enhancements and New Features

Tai-Sung Lee et al.

JOURNAL OF CHEMICAL INFORMATION AND MODELING (2018)

Article Multidisciplinary Sciences

Structure of the μ-opioid receptor-Gi protein complex

Antoine Koehl et al.

NATURE (2018)

Review Cell Biology

Mechanisms of signalling and biased agonism in G protein-coupled receptors

Denise Wootten et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2018)

Article Biochemistry & Molecular Biology

Structural determinants of 5-HT2B receptor activation and biased agonism

John D. McCorvy et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2018)

Article Biochemistry & Molecular Biology

G protein signaling-biased agonism at the κ-opioid receptor is maintained in striatal neurons

Jo-Hao Ho et al.

SCIENCE SIGNALING (2018)

Article Biochemical Research Methods

CHARMM36m: an improved force field for folded and intrinsically disordered proteins

Jing Huang et al.

NATURE METHODS (2017)

Article Medicine, General & Internal

The Role of Science in Addressing the Opioid Crisis

Nora D. Volkow et al.

NEW ENGLAND JOURNAL OF MEDICINE (2017)

Article Biochemistry & Molecular Biology

Crystal Structure of an LSD-Bound Human Serotonin Receptor

Daniel Wacker et al.

Article Multidisciplinary Sciences

Structure-based discovery of opioid analgesics with reduced side effects

Aashish Manglik et al.

NATURE (2016)

Article Biochemistry & Molecular Biology

Biased agonists of the kappa opioid receptor suppress pain and itch without causing sedation or dysphoria

Tarsis F. Brust et al.

SCIENCE SIGNALING (2016)

Article Biochemistry & Molecular Biology

Biased agonists of the kappa opioid receptor suppress pain and itch without causing sedation or dysphoria

Tarsis F. Brust et al.

SCIENCE SIGNALING (2016)

Article Chemistry, Physical

Long-Time-Step Molecular Dynamics through Hydrogen Mass Repartitioning

Chad W. Hopkins et al.

JOURNAL OF CHEMICAL THEORY AND COMPUTATION (2015)

Article Multidisciplinary Sciences

Structural insights into μ-opioid receptor activation

Weijiao Huang et al.

NATURE (2015)

Article Biochemistry & Molecular Biology

PRESTO-Tango as an open-source resource for interrogation of the druggable human GPCRome

Wesley K. Kroeze et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2015)

Article Biochemistry & Molecular Biology

PRESTO-Tango as an open-source resource for interrogation of the druggable human GPCRome

Wesley K. Kroeze et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2015)

Review Dermatology

Nalfurafine hydrochloride to treat pruritus: a review

Shigeki Inui

CLINICAL COSMETIC AND INVESTIGATIONAL DERMATOLOGY (2015)

Article Pharmacology & Pharmacy

The G Protein-Biased kappa-Opioid Receptor Agonist RB-64 Is Analgesic with a Unique Spectrum of Activities In Vivo

Kate L. White et al.

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS (2015)

Article Chemistry, Medicinal

Functionally Selective Dopamine D2, D3 Receptor Partial Agonists

Dorothee Moeller et al.

JOURNAL OF MEDICINAL CHEMISTRY (2014)

Article Pharmacology & Pharmacy

A G Protein-Biased Ligand at the μ-Opioid Receptor Is Potently Analgesic with Reduced Gastrointestinal and Respiratory Dysfunction Compared with Morphines

Scott M. DeWire et al.

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS (2013)

Article Biochemistry & Molecular Biology

A Simple Method for Quantifying Functional Selectivity and Agonist Bias

Terry Kenakin et al.

ACS CHEMICAL NEUROSCIENCE (2012)

Article Biochemistry & Molecular Biology

6′-Guanidinonaltrindole (6′-GNTI) Is a G Protein-biased κ-Opioid Receptor Agonist That Inhibits Arrestin Recruitment

Marie-Laure Rives et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2012)

Article Chemistry, Medicinal

Automation of the CHARMM General Force Field (CGenFF) II: Assignment of Bonded Parameters and Partial Atomic Charges

K. Vanommeslaeghe et al.

JOURNAL OF CHEMICAL INFORMATION AND MODELING (2012)

Article Chemistry, Medicinal

Automation of the CHARMM General Force Field (CGenFF) I: Bond Perception and Atom Typing

K. Vanommeslaeghe et al.

JOURNAL OF CHEMICAL INFORMATION AND MODELING (2012)

Article Multidisciplinary Sciences

Structure of the human κ-opioid receptor in complex with JDTic

Huixian Wu et al.

NATURE (2012)

Article Multidisciplinary Sciences

The allosteric vestibule of a seven transmembrane helical receptor controls G-protein coupling

Andreas Bock et al.

NATURE COMMUNICATIONS (2012)

Article Biochemical Research Methods

Features and development of Coot

P. Emsley et al.

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY (2010)

Article Biochemical Research Methods

PHENIX: a comprehensive Python-based system for macromolecular structure solution

Paul D. Adams et al.

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY (2010)

Article Anesthesiology

Delta and Kappa Opioid Receptors as Suitable Drug Targets for Pain

Todd W. Vanderah

CLINICAL JOURNAL OF PAIN (2010)

Article Chemistry, Physical

Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types

Jeffery B. Klauda et al.

JOURNAL OF PHYSICAL CHEMISTRY B (2010)

Article Biochemical Research Methods

Crystallizing membrane proteins using lipidic mesophases

Martin Caffrey et al.

NATURE PROTOCOLS (2009)

Article Chemistry, Multidisciplinary

Additive Empirical Force Field for Hexopyranose Monosaccharides

Olgun Guvench et al.

JOURNAL OF COMPUTATIONAL CHEMISTRY (2008)

Article Multidisciplinary Sciences

Two protonation switches control rhodopsin activation in membranes

Mohana Mahalingam et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2008)

Article Chemistry, Multidisciplinary

Phaser crystallographic software

Airlie J. McCoy et al.

JOURNAL OF APPLIED CRYSTALLOGRAPHY (2007)

Article Biochemical Research Methods

HKL-3000:: the integration of data reduction and structure solution -: from diffraction images to an initial model in minutes

Wladek Minor et al.

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY (2006)

Article Biochemical Research Methods

OPM: Orientations of proteins in membranes database

MA Lomize et al.

BIOINFORMATICS (2006)

Article Biochemistry & Molecular Biology

On the role of the crystal environment in determining protein side-chain conformations

MP Jacobson et al.

JOURNAL OF MOLECULAR BIOLOGY (2002)

Review Biochemistry & Molecular Biology

Gz signaling:: emerging divergence from Gi signaling

MKC Ho et al.

ONCOGENE (2001)

Article Pharmacology & Pharmacy

TRK-820, a selective κ-opioid agonist, produces potent antinociception in cynomolgus monkeys

T Endoh et al.

JAPANESE JOURNAL OF PHARMACOLOGY (2001)

Article Biochemistry & Molecular Biology

The effect of pH on β2 adrenoceptor function -: Evidence for protonation-dependent activation

P Ghanouni et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2000)