Review
Biochemistry & Molecular Biology
Mark E. Dumont, James B. Konopka
Summary: The Saccharomyces cerevisiae alpha-factor mating pheromone receptor (Ste2p) has been studied extensively to understand the mechanisms of G protein-coupled receptors. Genetic and biochemical strategies have been effective in revealing the structure-function relationship of Ste2p and its conformational changes upon activation. Recent cryo-EM structures provide valuable insights for studying other proteins.
Review
Pharmacology & Pharmacy
Xuesong Wang, Gerard J. P. van Westen, Laura H. Heitman, Adriaan P. IJzerman
Summary: G protein-coupled receptors (GPCRs) are the largest class of membrane proteins in the human genome, regulating various biological processes and serving as targets for a significant percentage of drugs on the market. Yeast serves as a useful model for studying GPCRs and offers opportunities for novel drug discovery.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Chemistry, Physical
Orkun Cevheroglu, Merve Murat, Sara Mingu-Akmete, Cagdas D. Son
Summary: The study revealed that the yeast mating pheromone GPCR Ste2p exists as a tetrameric complex at least on the plasma membrane, with a significant increase in FRET values in its active form.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Biochemistry & Molecular Biology
Yinjie Zhang, Boyang Jason Wu, Xiaolan Yu, Ping Luo, Hao Ye, Yan Yu, Wei Han, Jingjing Li
Summary: This study introduces a system called Antigen-Antibody Co-Display (AACD) that can rapidly detect the interactions between G-protein-coupled receptors (GPCRs) and their antibodies, while also identifying off-target antibodies and antibody-associated epitopes. The AACD system has the potential to improve the process of GPCR antibody development and provide a new strategy for GPCRs antibody screening.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Bettina Lengger, Emma E. Hoch-Schneider, Christina N. Jensen, Tadas Jakociunas, Anja A. Petersen, Thomas M. Frimurer, Emil Jensen, Michael K. Jensen
Summary: This study systematically assessed the signaling of various serotonin GPCRs and successfully achieved high-resolution quantification of serotonin using a yeast platform. The study also characterized serotonin GPCR polymorphisms in human populations and observed differences in signaling among these polymorphisms.
Review
Cell Biology
Haoran Jiang, Daniella Galtes, Jialu Wang, Howard A. Rockman
Summary: This review explores the signaling pathways, dynamic structures, and physiological relevance of the three most important GPCR signaling effectors in the cardiovascular system: heterotrimeric G proteins, GPCR kinases (GRKs), and 8-arrestins. It summarizes their prominent roles in GPCR pharmacology before transitioning into less well-explored areas. The application of new technologies has contributed to an increasing understanding of GPCR structure and downstream effectors.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Estefania Moreno, Nil Casajuana-Martin, Michael Coyle, Baruc Campos Campos, Ewa Galaj, Claudia Llinas del Torrent, Arta Seyedian, William Rea, Ning-Sheng Cai, Alessandro Bonifazi, Benjamin Floran, Zheng-Xiong Xi, Xavier Guitart, Vicent Casado, Amy H. Newman, Christopher Bishop, Leonardo Pardo, Sergi Ferre
Summary: This study provides evidence that heteromerization of G protein-coupled receptors (GPCRs), specifically dopamine D1 and D3 receptors, can influence the pharmacological properties of selective ligands. In vivo experiments support the involvement of D1R-D3R heteromers in the development of L-DOPA-induced dyskinesia in Parkinson's disease, suggesting the potential of targeting GPCR heteromers for drug development.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Juergen Einsiedel, Maximilian F. Schmidt, Harald Huebner, Peter Gmeiner
Summary: A broadly applicable synthesis method was developed for peptides incorporating mixed disulfides between cysteine and homocysteine and cysteamine. The method was successfully applied to pharmacologically relevant GPCR ligands and showed covalent binding to neurotensin receptor 1 in a radioligand depletion study.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Bui San Thai, Ling Yeong Chia, Anh T. N. Nguyen, Chengxue Qin, Rebecca H. Ritchie, Dana S. Hutchinson, Andrew Kompa, Paul J. White, Lauren T. May
Summary: Heart failure remains a significant cause of morbidity and mortality worldwide. Current treatment options have limitations, leading to many patients progressing to advanced stages. Exploration of novel therapeutics targeting G protein-coupled receptors (GPCRs) has shown promise, but efficacy and unwanted effects remain as challenges.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Mydirah Littlepage-Saunders, Michael J. Hochstein, Doris S. Chang, Kari A. Johnson
Summary: Dopamine transmission in the striatum is regulated by various G protein-coupled receptors (GPCRs) that bind neuromodulators, including dopamine itself. These GPCRs can modulate dopamine release by acting on different components of the dopaminergic circuitry and can have distinct effects on behavior and psychoactive drug actions. This review discusses the mechanisms by which GPCRs regulate dopaminergic transmission and their relevance to the effects of psychoactive drugs on physiology and behavior.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Damian Jacenik, Pawel Hikisz, Ellen J. Beswick, Jakub Fichna
Summary: Among the various adhesion G protein-coupled receptors, ADGRF5 stands out with its unique domains in the N-terminal tail that play a critical role in cell-cell and cell-matrix interactions, as well as cell adhesion. Although the biology of ADGRF5 is still not fully understood, accumulating evidence suggests its fundamental importance in both health and disease. Recent studies have highlighted its potential diagnostic value in osteoporosis and cancers, and ongoing research indicates its relevance to other diseases as well. This article provides a comprehensive overview of the current understanding of ADGRF5 in human disease physiology and pathophysiology, emphasizing its potential as a novel therapeutic target in various areas.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Raudah Lazim, Donghyuk Suh, Jai Woo Lee, Thi Ngoc Lan Vu, Sanghee Yoon, Sun Choi
Summary: The presence of GPCR dimers has sparked research into their importance in disease pathogenesis and drug design, uncovering new signaling pathways and potential therapeutic targets. The increasing influence of computational methods in research is providing new avenues for understanding the functions and interactions of GPCRs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Alastair C. Keen, Manuela Jorg, Michelle L. L. Halls
Summary: The ubiquitin-proteasome system is a major pathway for protein degradation in cells, and methods have been developed to exploit this system for targeted protein degradation. Targeted protein degraders have been useful tools in discovery research and are being developed as therapeutics. However, most targeted protein degrader technologies have been developed for cytosolic proteins, while examples for G protein-coupled receptor (GPCR) degradation are limited. This review discusses the strategies used for applying targeted protein degradation to GPCRs and explores alternative approaches used for degrading other integral membrane proteins.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Rina Pokhrel, Alexandra L. Morgan, Harley R. Robinson, Martin J. Stone, Simon R. Foster
Summary: G protein-coupled receptor (GPCR) activation triggers complex intracellular signalling networks, which have important implications for receptor biology and drug discovery. Phosphoproteomics has emerged as a powerful tool for investigating these networks and accelerating the discovery of new therapeutic targets.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shuai Luo, Peng Zhang, Wei Miao, Jie Xiong
Summary: This study provides the first comprehensive genome-wide identification of GPCRs in ciliates, identifying 492 GPCRs in 24 ciliates. GPCRs in ciliates can be assigned to four families, with most belonging to family A. Gene duplication events play a role in the expansion of the GPCR superfamily in ciliates. This study improves our understanding of the evolution and function of GPCRs in ciliates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)