Review
Immunology
Yi Wang, Cheng-long Zhu, Peng Li, Qiang Liu, Hui-ru Li, Chang-meng Yu, Xiao-ming Deng, Jia-feng Wang
Summary: Sepsis is a life-threatening dysfunction caused by an uncontrolled host response to infection, leading to respiratory dysfunction and acute respiratory distress syndrome (ARDS). Neutrophils, the first line of defense against infection, play a major role in sepsis. However, studies have shown that despite high levels of chemokines at the site of infection, neutrophils cannot migrate properly and instead accumulate in the lungs, causing tissue damage and ARDS. Dysregulation of chemokine receptors, particularly G protein-coupled receptors (GPCRs), is implicated in impaired neutrophil migration. This review summarizes the signaling pathways and mechanisms by which GPCR dysfunction in sepsis leads to impaired neutrophil chemotaxis and proposes potential targets for intervention to improve neutrophil chemotaxis.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biology
Fumiya K. Sano, Hiroaki Akasaka, Wataru Shihoya, Osamu Nureki, David Drew
Summary: This study reports the structure of the complex between the endothelin ETB receptor and G-protein, revealing how endothelin activates the ETB receptor and expanding the diversity of G-protein binding modes.
Article
Multidisciplinary Sciences
Anjie Xia, Xihao Yong, Changbin Zhang, Guifeng Lin, Guowen Jia, Chang Zhao, Xin Wang, Yize Hao, Yifei Wang, Pei Zhou, Xin Yang, Yue Deng, Chao Wu, Yujiao Chen, Jiawei Zhu, Xiaodi Tang, Jingming Liu, Shiyu Zhang, Jiahao Zhang, Zheng Xu, Qian Hu, Jinlong Zhao, Yuting Yue, Wei Yan, Zhaoming Su, Yuquan Wei, Rongbin Zhou, Haohao Dong, Zhenhua Shao, Shengyong Yang
Summary: This study presents the cryo-EM structures of GPR34 bound with LysoPS and its inhibition by the antagonist YL-365. The findings provide mechanistic insights into the endogenous agonist recognition and antagonist inhibition of GPR34, highlighting GPR34 as a promising target for disease treatment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Medicinal
Thanigaimalai Pillaiyar, Francesca Rosato, Monika Wozniak, Jeremy Blavier, Maelle Charles, Celine Laschet, Thales Kronenberger, Christa E. Mueller, Julien Hanson
Summary: This study identified a selective GPR27 agonist and a series of new derivatives and analogs, including potent agonists with higher efficacies than the lead compound. Docking studies predicted the putative binding site and interactions of an agonist with GPR27, providing important new tools for further characterizing the (patho)physiological roles of GPR27.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Thian-Sze Wong, Wei Gao, Geng Chen, Chen Qiu, Guodong He, Fang Ye, Zhangsong Wu, Zicheng Zeng, Yang Du
Summary: GPR21 is a class A orphan GPCR associated with developing T2DM. Cryo-EM and single-particle analysis revealed the high-resolution structure of GPR21-G alpha s complexes, providing direct evidence of their coupling at physiological conditions. Mutagenesis and biochemical analysis showed that ECL2 of GPR21 is essential for transducing intracellular signals via cAMP.
Article
Medicine, Research & Experimental
Fang Ye, Thian-Sze Wong, Geng Chen, Zhiyi Zhang, Binghao Zhang, Shiyi Gan, Wei Gao, Jiancheng Li, Zhangsong Wu, Xin Pan, Yang Du
Summary: The study elucidated the activation mechanism of GPR17-Gi complex, revealing the self-activation mechanism of GPR17 and the interaction of Gi with key residues in GPR17.
Article
Biochemical Research Methods
Jooseong Oh, Hyi-Thaek Ceong, Dokyun Na, Chungoo Park
Summary: In this study, a machine learning model was developed to identify GPCR agonists and antagonists. The model showed high accuracy in classifying ligands and can be applied in virtual screening for potential GPCR-binding agonists and antagonists.
BMC BIOINFORMATICS
(2022)
Article
Medicine, General & Internal
Gerd Wallukat, Stephan Mattecka, Katrin Wenzel, Wieland Schroedl, Birgit Vogt, Patrizia Brunner, Ahmed Sheriff, Rudolf Kunze
Summary: This study found that C-reactive protein (CRP) affects intracellular calcium signaling and blood pressure. When CRP is combined with GPCR agonists in cardiomyocytes, it can interfere with the desensitization of GPCRs, regardless of the type of GPCR, but dependent on the concentration of CRP.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Pharmacology & Pharmacy
Sara Marsango, Graeme Milligan
Summary: GPR84 is a little-studied receptor that belongs to the rhodopsin-like class A G protein-coupled receptors, but it has attracted attention for its therapeutic potential. Its expression is up-regulated in response to acute inflammation and in inflammatory diseases, and activation of the receptor is involved in regulating pro-inflammatory responses and cell migration of the innate immune system. While GPR84 primarily signals through G(alpha i/o)-proteins, there is evidence that it can also recruit arrestin proteins upon agonist activation, which affects receptor internalization and desensitization. However, the phosphorylation patterns of GPR84 and their role in these processes are not well understood.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Yao Lu, Cassandra J. Hatzipantelis, Christopher J. Langmead, Gregory D. Stewart
Summary: Schizophrenia treatment currently relies on outdated science, and targeting dopamine receptors has limited efficacy and side effects. Non-dopaminergic GPCR-targeting drugs show promise but have not yet been successfully developed for clinical use. Recent attention has focused on non-dopaminergic GPCR-targeting drugs, which have demonstrated efficacy in certain symptoms of schizophrenia.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Nutrition & Dietetics
Elena Jimenez-Marti, Gema Hurtado-Genoves, Maria Aguilar-Ballester, Sergio Martinez-Hervas, Herminia Gonzalez-Navarro
Summary: The increasing prevalence of obesity and type 2 diabetes is causing a socioeconomic burden, particularly in the form of cardiovascular disease. Metabolic surgery, which improves the action of preproglucagon-derived hormones, shows promise beyond traditional dietary restrictions and weight loss. This review explores the complexities of these hormones and their analogues, particularly the use of dual and triagonists, and discusses their potential for treating cardiovascular disease.
Article
Biochemistry & Molecular Biology
Ikko Nureki, Kazuhiro Kobayashi, Tatsuki Tanaka, Kanae Demura, Asuka Inoue, Wataru Shihoya, Osamu Nureki
Summary: This study reported the cryoelectron microscopy structures of beta(3)-adrenergic receptor (beta(3)AR) in complex with selective agonist solabegron and nonselective agonist isoproterenol. The structural analysis revealed the conformational changes of extracellular loop 2 depending on the bound agonist and the narrow exosite of beta(3)AR, which explains the receptor's preference for specific agonists with elongated shapes. This study deepens the understanding of beta(3)AR agonist binding characteristics and has implications for the development of selective drugs.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Steven D. E. Fried, Kushani S. K. Hewage, Anna R. Eitel, Audrey Struts, Nipuna Weerasinghe, Suchithranga M. D. C. Perera, Michael F. Brown
Summary: Maltose activates rhodopsin and enters the protein bound to water, facilitating GPCR signaling. This study challenges the understanding of the role of water molecules in GPCR signaling mechanisms.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Medicinal
Yuxin Shi, Yi Chen, Liping Deng, Kui Du, Shaoyong Lu, Ting Chen
Summary: This article summarizes the known structural complexes of G protein-coupled receptors (GPCRs) bound to peptide ligands, with a focus on the interactions between the receptor and its peptide ligand at the orthosteric site. In-depth structural investigations have provided valuable insights into the molecular mechanisms underlying peptide recognition, contributing to the discovery of GPCR peptide drugs with improved therapeutic effects.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Jeanette M. Einspahr, Douglas G. Tilley
Summary: Adhesion GPCRs, as the second-largest family of GPCRs, have not yet been targeted for clinical treatment despite increasing evidence of their physiological and pathological functions. They are associated with a variety of diseases, including cancer, central nervous system disorders, immunity, and inflammation.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)