☆ 4.8 Article

Structure and Molecular Mechanism of Signaling for the Glucagon-like Peptide-1 Receptor Bound to Gs Protein and Exendin-P5 Biased Agonist

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2023)

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)

添加到收藏夹

Article Biochemistry & Molecular Biology

TmAlphaFold database: membrane localization and evaluation of AlphaFold2 predicted alpha-helical transmembrane protein structures

Laszlo Dobson et al.

Summary: AI-driven protein structure prediction, particularly AlphaFold2, has significant implications in the field of structural biology, especially for transmembrane proteins. The TmAlphaFold database provides a valuable tool for accurately assessing protein localization and structure.

NUCLEIC ACIDS RESEARCH (2023)

添加到收藏夹

Article Chemistry, Multidisciplinary

The dynamics of agonist-β2-adrenergic receptor activation induced by binding of GDP-bound Gs protein

Amirhossein Mafi et al.

Summary: In this study, molecular metadynamics computations were used to predict the mechanism of activation of the beta(2)-adrenergic receptor (beta(2)AR) and its cognate Gs protein by an agonist. It was found that attaching the inactive Gs protein to the agonist-bound inactive beta(2)AR can lead to activation of the Gs protein by breaking the ionic lock in the beta(2)AR. Activation of the Gs protein results in opening of the GDP binding pocket and expansion of G alpha s-alpha 5 in the beta(2)AR cytoplasmic region.

NATURE CHEMISTRY (2023)

添加到收藏夹

Article Biochemistry & Molecular Biology

Structural and functional diversity among agonist-bound states of the GLP-1 receptor

Brian P. Cary et al.

Summary: Recent advances in understanding the structures of G-protein-coupled receptors (GPCRs) have highlighted the importance of conformational flexibility in signal propagation. By studying the activation of the GLP-1 receptor, it was found that the conformational plasticity of peptide agonists plays a crucial role in determining agonist efficacy.

NATURE CHEMICAL BIOLOGY (2022)

添加到收藏夹

Review Pharmacology & Pharmacy

Structural perspective of class B1 GPCR signaling

Zhaotong Cong et al.

Summary: Class B1 G protein-coupled receptors have important functions in human physiology and disease pathology. Recent advances in cryo-electron microscopy and X-ray crystallography have provided detailed insights into their three-dimensional structures, ligand recognition, and receptor activation. These findings offer new avenues for developing improved therapeutic agents.

TRENDS IN PHARMACOLOGICAL SCIENCES (2022)

添加到收藏夹

Article Multidisciplinary Sciences

Dynamics of GLP-1R peptide agonist engagement are correlated with kinetics of G protein activation

Giuseppe Deganutti et al.

Summary: This study investigates the mechanism and consequences of GLP-1R binding to four peptide agonists. The results reveal that distinctions in peptide N-terminal interactions and dynamics with the GLP-1R transmembrane domain are reciprocally associated with differences in the allosteric coupling to G proteins.

NATURE COMMUNICATIONS (2022)

添加到收藏夹

Article Multidisciplinary Sciences

Structural determinants of dual incretin receptor agonism by tirzepatide

Bingfa Sun et al.

Summary: Tirzepatide is a dual incretin receptor agonist that improves glucose control and body weight regulation in type 2 diabetes mellitus. Mechanistic pharmacology studies combined with cryogenic electron microscopy have provided insights into the structural basis and interactions of Tirzepatide with GIPR and GLP-1R.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

添加到收藏夹

Article Multidisciplinary Sciences

Structural insights into multiplexed pharmacological actions of tirzepatide and peptide 20 at the GIP, GLP-1 or glucagon receptors

Fenghui Zhao et al.

Summary: This study describes the cryo-EM structures of tirzepatide-bound GIPR and GLP-1R, as well as peptide 20-bound GIPR, GLP-1R, and GCGR, revealing the molecular basis of their multiplexed pharmacological actions. Multi-targeting agonists at GIPR, GLP-1R, or GCGR are crucial for the treatment of type 2 diabetes and obesity, showing potential value in clinical trials.

NATURE COMMUNICATIONS (2022)

添加到收藏夹

Article Multidisciplinary Sciences

Ligand recognition and biased agonism of the D1 dopamine receptor

Xiao Teng et al.

Summary: This study presents three cryo-electron microscopy structures of the D1 dopamine receptor (D1R)-Gs complex bound to three distinct D1R-selective drugs. The findings reveal the importance of drug binding modes for biased signaling.

NATURE COMMUNICATIONS (2022)

添加到收藏夹

Article Biochemistry & Molecular Biology

Cryo-EM structure of the dual incretin receptor agonist, peptide-19, in complex with the glucagon-like peptide-1 receptor

Rachel M. Johnson et al.

Summary: Dual agonists that can activate both GLP-1R and GIPR have high efficacy in treating metabolic disease, with peptide-19 being a potent prototype. The complex of peptide-19:GLP-1R:Gs exhibits a more open binding pocket and high dynamicity in the TM binding pocket. This structure provides unique insights into GLP-1R activation by this dual agonist.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2021)

添加到收藏夹

Article Multidisciplinary Sciences

Highly accurate protein structure prediction with AlphaFold

John Jumper et al.

Summary: Proteins are essential for life, and accurate prediction of their structures is a crucial research problem. Current experimental methods are time-consuming, highlighting the need for accurate computational approaches to address the gap in structural coverage. Despite recent progress, existing methods fall short of atomic accuracy in protein structure prediction.

NATURE (2021)

添加到收藏夹

Article Multidisciplinary Sciences

Routine sub-2.5Å cryo-EM structure determination of GPCRs

Radostin Danev et al.

Summary: There is a need to optimize cryo-EM data acquisition approaches to improve the resolution of GPCR cryo-EM structures to better than 2.5 angstrom, in order to use them for structure-based drug design purposes. The authors present a systematic analysis of the main cryo-EM experimental parameters using three GPCRs as test cases, which is also of interest for the cryo-EM structure determination of other small membrane proteins.

NATURE COMMUNICATIONS (2021)

添加到收藏夹

Article Cell Biology

Structure and dynamics of semaglutide- and taspoglutide-bound GLP-1R-Gs complexes

Xin Zhang et al.

Summary: GLP-1R agonists play a crucial role in the treatment of diabetes and obesity, but a lack of structural information limits the understanding of their molecular mechanisms. Studies have shown that semaglutide and taspoglutide have similar peptide interactions with GLP-1R, but exhibit different motions between the receptor and bound peptides.

CELL REPORTS (2021)

添加到收藏夹

Article Chemistry, Medicinal

GLP-1 Val8: A Biased GLP-1R Agonist with Altered Binding Kinetics and Impaired Release of Pancreatic Hormones in Rats

Wijnand J. C. van der Velden et al.

Summary: Biased ligands are pharmacologically important for reducing on-target side effects and improving drug efficacy. This study investigated the effects of a N-terminal modification in GLP-1 on GLP-1 receptor signaling, revealing significant impairments in internalization and alterations in molecular pharmacological properties. The findings suggest that subtle changes in the N-terminus of GLP-1 can induce profound differences in therapeutic targeting of the GLP-1 system, which may facilitate the development of optimized GLP-1R agonists.

ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE (2021)

添加到收藏夹

Review Biochemistry & Molecular Biology

G protein-coupled receptors: structure- and function-based drug discovery

Dehua Yang et al.

Summary: Recent progress in understanding the structure-function relationships of G protein-coupled receptors has accelerated drug development significantly. This article aims to provide a comprehensive overview of this important field to a broader readership interested in drug discovery.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

添加到收藏夹

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)

添加到收藏夹

Article Multidisciplinary Sciences

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

Carl-Mikael Suomivuori et al.

SCIENCE (2020)

添加到收藏夹

Review Cell Biology

Conformational Basis of G Protein-Coupled Receptor Signaling Versatility

Laura M. Wingler et al.

TRENDS IN CELL BIOLOGY (2020)

添加到收藏夹

Article Biochemistry & Molecular Biology

Differential GLP-1R Binding and Activation by Peptide and Non-peptide Agonists

Xin Zhang et al.

MOLECULAR CELL (2020)

添加到收藏夹

Article Biochemistry & Molecular Biology

Structure of an endosomal signaling GPCR-G protein-β-arrestin megacomplex

Anthony H. Nguyen et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2019)

添加到收藏夹

Article Biochemistry & Molecular Biology

Angiotensin Analogs with Divergent Bias Stabilize Distinct Receptor Conformations

Laura M. Wingler et al.

CELL (2019)

添加到收藏夹

Article Biochemistry & Molecular Biology

Structure-inspired design of β-arrestin-biased ligands for aminergic GPCRs

John D. McCorvy et al.

NATURE CHEMICAL BIOLOGY (2018)

添加到收藏夹

Article Multidisciplinary Sciences

Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor-Gs complex

Yi-Lynn Liang et al.

NATURE (2018)

添加到收藏夹

Review Cell Biology

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

Denise Wootten et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2018)

添加到收藏夹

Review Chemistry, Medicinal

Rules of Engagement: GPCRs and G Proteins

Alisa Glukhova et al.

ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE (2018)

添加到收藏夹

Review Chemistry, Multidisciplinary

GPCR Dynamics: Structures in Motion

Naomi R. Latorraca et al.

CHEMICAL REVIEWS (2017)

添加到收藏夹

Review Chemistry, Multidisciplinary

Allostery and Biased Agonism at Class B G Protein-Coupled Receptors

Denise Wootten et al.

CHEMICAL REVIEWS (2017)

添加到收藏夹

Article Biochemical Research Methods

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

Jing Huang et al.

NATURE METHODS (2017)

添加到收藏夹

Article Multidisciplinary Sciences

Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein

Yan Zhang et al.

NATURE (2017)

添加到收藏夹

Article Biotechnology & Applied Microbiology

Trends in GPCR drug discovery: new agents, targets and indications

Alexander S. Hauser et al.

NATURE REVIEWS DRUG DISCOVERY (2017)

添加到收藏夹

Article Pharmacology & Pharmacy

Characterization of signal bias at the GLP-1 receptor induced by backbone modification of GLP-1

Marlies V. Hager et al.

BIOCHEMICAL PHARMACOLOGY (2017)

添加到收藏夹

Article Chemistry, Physical

CHARMM-GUI Input Generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM Simulations Using the CHARMM36 Additive Force Field

Jumin Lee et al.

JOURNAL OF CHEMICAL THEORY AND COMPUTATION (2016)

添加到收藏夹

Review Pharmacology & Pharmacy

Glucagon-Like Peptide-1 and Its Class B G Protein-Coupled Receptors: A Long March to Therapeutic Successes

Chris de Graaf et al.

PHARMACOLOGICAL REVIEWS (2016)

添加到收藏夹

Article Multidisciplinary Sciences

Autocrine selection of a GLP-1R G-protein biased agonist with potent antidiabetic effects

Hongkai Zhang et al.

NATURE COMMUNICATIONS (2015)

添加到收藏夹

Review Pharmacology & Pharmacy

Structure of Class B GPCRs: new horizons for drug discovery

Andrea Bortolato et al.

BRITISH JOURNAL OF PHARMACOLOGY (2014)

添加到收藏夹

Article Chemistry, Multidisciplinary

CHARMM-GUI Membrane Builder Toward Realistic Biological Membrane Simulations

Emilia L. Wu et al.

JOURNAL OF COMPUTATIONAL CHEMISTRY (2014)

添加到收藏夹

Article Multidisciplinary Sciences

Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs

Ron O. Dror et al.

NATURE (2013)

添加到收藏夹

Article Pharmacology & Pharmacy

Differential Activation and Modulation of the Glucagon-Like Peptide-1 Receptor by Small Molecule Ligands

Denise Wootten et al.

MOLECULAR PHARMACOLOGY (2013)

添加到收藏夹

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)

添加到收藏夹

Article Pharmacology & Pharmacy

Allosteric Ligands of the Glucagon-Like Peptide 1 Receptor (GLP-1R) Differentially Modulate Endogenous and Exogenous Peptide Responses in a Pathway-Selective Manner: Implications for Drug Screening

Cassandra Koole et al.

MOLECULAR PHARMACOLOGY (2010)

添加到收藏夹

Article Chemistry, Physical

Flat-Bottom Strategy for Improved Accuracy in Protein Side-Chain Placements

Victor Wai Tak Kam et al.

JOURNAL OF CHEMICAL THEORY AND COMPUTATION (2008)

添加到收藏夹

Article Chemistry, Multidisciplinary

Software news and updates - CHARNIM-GUI: A web-based grraphical user interface for CHARMM

Sunhwan Jo et al.

JOURNAL OF COMPUTATIONAL CHEMISTRY (2008)

添加到收藏夹

Article Biochemistry & Molecular Biology

Peptide binding at the GLP-1 receptor

R. Mann et al.

BIOCHEMICAL SOCIETY TRANSACTIONS (2007)

添加到收藏夹

© Peeref 2019-2024. All rights reserved.