Review
Chemistry, Multidisciplinary
Xin-heng He, Chong-zhao You, Hua-liang Jiang, Yi Jiang, H. Eric Xu, Xi Cheng
Summary: G protein-coupled receptors (GPCRs) are important drug targets that play crucial roles in various physiological processes. Although extensive efforts have been made in the field of structural biology, a significant number of GPCR structures remain unsolved due to their structural instability. Recently, AlphaFold2 has been developed as a tool to predict the structure models of GPCRs and other functionally important proteins. However, our evaluation reveals several differences between the predicted models and experimental structures, such as the assembly of domains, shape of ligand-binding pockets, and conformation of binding interfaces. These differences hinder the use of predicted structure models in functional studies and structure-based drug design, where reliable high-resolution structural information is required.
ACTA PHARMACOLOGICA SINICA
(2023)
Review
Cell Biology
Marta Lagana, Geraldine Schlecht-Louf, Francoise Bachelerie
Summary: GRKs not only regulate GPCR desensitization, but also act as scaffolds and signaling adapters in complex signaling networks that affect immune cell migration. The coordinated docking of multiple GRKs on an active chemokine receptor determines a specific receptor phosphorylation barcode that translates into different signaling and migration outcomes.
Review
Medicine, Research & Experimental
Juan Carlos Martinez-Morales, K. Helivier Solis, M. Teresa Romero-Avila, Guadalupe Reyes-Cruz, J. Adolfo Garcia-Sainz
Summary: G protein-coupled receptors (GPCRs) are membrane proteins that function as sensors and play significant roles in various physiological and pathological processes. This review provides an overview of the current understanding of the structure, signaling, internalization, and recycling of GPCRs.
ARCHIVES OF MEDICAL RESEARCH
(2022)
Review
Endocrinology & Metabolism
Fanhua Wang, Mingyao Liu, Ning Wang, Jian Luo
Summary: This review discusses the role of G-protein coupled receptors (GPCRs) in osteoarthritis (OA), including the pathophysiological processes involved, preclinical and clinical trial data, and the challenges in developing therapies targeting GPCRs for OA.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mingcheng Qian, Zhengyang Sun, Xin Chen, Serge Van Calenbergh
Summary: This review provides an overview of the design strategy of bivalent ligands for G protein-coupled receptors (GPCRs) and mainly focuses on their application in studying and detecting GPCR dimerization in vitro and in vivo. Bivalent ligands have specific properties and are capable of binding to GPCR homodimers or heterodimers simultaneously, showing specific signal transduction compared to monovalent ligands.
BIOORGANIC CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Bastian Heim, Rene Handrick, Marcus D. Hartmann, Hans Kiefer
Summary: This study presents a generic approach to assess and optimize GPCR refolding from E. coli inclusion bodies through thermostability analysis. By adapting a technique based on cysteins exposed upon thermal denaturation with fluorescent dye CPM, successful expression, purification and refolding of GPCRs S1P(1) and GPR3 were demonstrated. Refolded receptors were then subjected to lipidic cubic phase crystallization screening.
Review
Pharmacology & Pharmacy
Kate F. Byrne, Ajay Pal, James F. Curtin, John C. Stephens, Gemma K. Kinsella
Summary: The focus of the review is on G-protein-coupled receptor (GPCR) targets, with chemokine, cannabinoid, and dopamine receptors showing promise. Further research is needed on potential targets such as MC4R, adhesion receptors, LPA, and Smo receptors to develop new drug-screening strategies for safe and effective GBM therapies.
DRUG DISCOVERY TODAY
(2021)
Review
Biochemistry & Molecular Biology
Dekel David, Ziv Bentulila, Merav Tauber, Yair Ben-Chaim
Summary: GPCRs are involved in signal transduction processes, and although they span the cell membrane, they have not been considered to be regulated by membrane potential. Recent studies, however, have shown that several GPCRs are voltage regulated. This review discusses the advances in understanding the voltage dependence of GPCRs, the suggested molecular mechanisms, and the possible physiological roles.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Reid H. J. Olsen, Justin G. English
Summary: Enzymatic and cellular signaling biosensors are powerful tools for understanding complex biological systems. G protein-coupled receptors (GPCRs) are extensively studied using biosensors, which have expanded our knowledge of this important class of proteins. Transducer biosensors that measure receptor coupling and selectivity, with a focus on receptor association and activation of heterotrimeric signaling complexes, are of particular importance.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Mark T. Agasid, Lars Sorensen, Leonhard H. Urner, Jun Yan, Carol Robinson
Summary: The use of mass spectrometry to study G protein-coupled receptors has revealed insights into sodium binding and ligand-induced changes, providing valuable information for understanding GPCR function.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biology
Ramon Cierco Jimenez, Nil Casajuana-Martin, Adrian Garcia-Recio, Lidia Alcantara, Leonardo Pardo, Mercedes Campillo, Angel Gonzalez
Summary: The study analyzed 119,069 natural variants in human olfactory receptors, revealing a significant diversity of natural variations in the olfactory gene repertoire between individuals and populations, with a considerable number of changes occurring at the structurally conserved regions. Mutations in positions linked to the conserved GPCR activation mechanism were highlighted, which could imply phenotypic variation in olfactory perception.
Review
Pharmacology & Pharmacy
Sergi Ferre, Francisco Ciruela, Carmen W. Dessauer, Javier Gonzalez-Maeso, Terence E. Hebert, Ralf Jockers, Diomedes E. Logothetis, Leonardo Pardo
Summary: The study proposes the concept of GPCR-effect assemblies (GEMMAs), which are pre-assembled before receptor activation and allow more efficient interactions between specific signaling components. This offers an alternative model to the conventional collision coupling model and explains the differential properties of GPCRs in different cellular environments.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Chemistry, Medicinal
Toni Kline, Cong Xu, Faith R. Kreitzer, Dow P. Hurst, Khalil M. Eldeeb, Jim Wager-Miller, Kathleen Olivas, Seon A. Hepburn, John W. Huffman, Ken Mackie, Allyn C. Howlett, Patricia Reggio, Nephi Stella
Summary: The author synthesized fourteen novel alkylindole analogues and evaluated their activities at alkylindole-sensitive GPCRs. They found three characteristics that favor binding to alkylindole-sensitive GPCRs versus CB1R/CB2R and identified novel chemical tools for studying alkylindole-sensitive GPCRs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Wojciech Pietrus, Rafal Kurczab, Dagmar Stumpfe, Andrzej J. Bojarski, Juergen Bajorath
Summary: The study showed that introducing fluorine can significantly increase ligand potency, but the effect of fluorination on affinity varies depending on the fluorination position. Fluorination of the aromatic ring at the ortho position is favorable for potency enhancement, while fluorination of aliphatic fragments more often leads to a decrease in biological activity.
Article
Chemistry, Multidisciplinary
Yunfang Xiong, Ran Ke, Qingyu Zhang, Wenjun Lan, Wanjun Yuan, Karol Nga Ieng Chan, Tom Roussel, Yifan Jiang, Jing Wu, Shuai Liu, Alice Sze Tsai Wong, Joong Sup Shim, Xuanjun Zhang, Ruiyu Xie, Nelson Dusetti, Juan Iovanna, Nagy Habib, Ling Peng, Leo Tsz On Lee
Summary: This study reports the effective modulation of a GPCR for cancer treatment using small activating RNAs (saRNAs) for the first time. The saRNAs promote the expression of MAS1, a GPCR that counteracts cancer cell proliferation and migration. By enhancing MAS1 expression, these saRNAs suppress tumorigenesis and inhibit tumor progression in multiple cancer models. This research not only provides a new strategy for cancer therapy by targeting the renin-angiotensin system, but also offers a new avenue to modulate GPCR signaling through RNA activation.
Article
Agriculture, Dairy & Animal Science
H. -J. Zhang, Z. -H. Cui, M. Liu, T. -Q. Min, X. Xiao, Z. -Q. Wang, Y. -X. Tao
Summary: The study investigated three naturally occurring mutations in chicken MC3R and found significant defects in receptor pharmacology for G104S and L151R, while the mechanism of action for M54L remains to be further explored.
DOMESTIC ANIMAL ENDOCRINOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Li-Kun Yang, Zhi-Shuai Hou, Ya-Xiong Tao
Summary: GPCRs are crucial in transmitting extracellular signals and regulating physiological functions. Mutations in GPCRs can lead to diseases and studying biased agonism provides insights into disease pathogenesis.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Ren-Lei Ji, Ya-Xiong Tao
Summary: Two new human MRAP2 splice variants were identified in this study, and the effects of MRAP1 and MRAP2 on MC3R and MC4R were investigated. The results suggest that MRAPs play important roles in the signaling and regulation of neural MC3R and MC4R.
Article
Chemistry, Medicinal
Luis E. Gimenez, Terry A. Noblin, Savannah Y. Williams, Satarupa Mullick Bagchi, Ren-Lei Ji, Ya-Xiong Tao, Claus B. Jeppesen, Kilian W. Conde-Frieboes, Tomi K. Sawyer, Paolo Grieco, Roger D. Cone
Summary: Peptides containing DNal(2 ')7, reported as MC3R subtype-specific agonists, were found to lack MC3R agonist activity. The cell lines used for pharmacological characterization were mischaracterized in terms of receptor subtype expression. Furthermore, peptides containing DNal(2 ')7 primarily exhibit antagonism of MC3R and MC4R.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Endocrinology & Metabolism
Huifei Sophia Zheng, Jeffrey G. Daniel, Julia M. Salamat, Laci Mackay, Chad D. Foradori, Robert J. Kemppainen, Satyanarayana R. Pondugula, Ya-Xiong Tao, Chen-Che Jeff Huang
Summary: This study investigated the early transcriptomic responses to dexamethasone (Dex) stimulation in vitro and in vivo, showing that there were distinct differences in the gene expression patterns. The adrenal glands of mice treated with Dex for 1 hour showed a strong association with the development of neuronal cells, indicating a rapid response to Dex in the adrenal medulla. However, in the Y-1 cell line, only a small proportion of genes exhibited differential expression after 1 hour of Dex treatment, and their expression returned to basal levels after 24 hours.
ENDOCRINE CONNECTIONS
(2022)
Review
Biochemistry & Molecular Biology
Li-Qin Ji, Ye Hong, Ya-Xiong Tao
Summary: MC5R is a unique melanocortin receptor with distinct tissue expression patterns, pharmacological properties, and physiological functions. It is widely distributed in both the central nervous system and peripheral tissues and is associated with lipid production, sexual behavior, immunomodulation, and energy metabolism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Endocrinology & Metabolism
Alfredo Ulloa-Aguirre, Teresa Zarinan, Ruben Gutierrez-Sagal, Ya-Xiong Tao
Summary: This article discusses the folding and trafficking of GPCRs involved in endocrine diseases, as well as experimental approaches to correct their misfolding, with a particular focus on the promising use of pharmacological chaperones.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Xiao-Chen Yuan, Ya-Xiong Tao
Summary: The discovery of melanocortins and their receptors has led to extensive research over the past 100 years, with particular focus on the neural melanocortin receptors' role in regulating energy homeostasis and potential therapeutic applications for treating metabolic conditions.
Article
Biochemistry & Molecular Biology
Ren-Lei Ji, Shan-Shan Jiang, Ya-Xiong Tao
Summary: The neural melanocortin receptors (MCRs) and their accessory proteins MRAP1 and MRAP2 play crucial roles in regulating energy homeostasis. This study reveals that MRAP1 and MRAP2s have species-specific effects on canine neural MCRs, providing a better understanding of their regulation.
Article
Endocrinology & Metabolism
Li-Qin Ji, Ying-Zhu Rao, Yong Zhang, Rong Chen, Ya-Xiong Tao
Summary: In this study, the orange-spotted grouper's Mc5r gene was cloned and its pharmacological characteristics were investigated. Four ligands were found to bind to Mc5r, increasing intracellular cAMP levels. Mrap2 was found to regulate the surface expression and activity of Mc5r. This study provides new insights into the pharmacology and regulation of fish Mc5r.
GENERAL AND COMPARATIVE ENDOCRINOLOGY
(2023)
Editorial Material
Endocrinology & Metabolism
Xiao-Chen Yuan, Ya-Xiong Tao
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Agriculture, Dairy & Animal Science
Yang Li, Wei-Jia Song, Shao-Kui Yi, Hui-Xia Yu, Hao-Lin Mo, Ming-Xing Yao, Ya-Xiong Tao, Li-Xin Wang
Summary: This study cloned and characterized the GPR84 gene in grass carp and found that it is responsive to medium-chain fatty acids and DIM. The expression of GPR84 in grass carp is high in the liver and spleen.
Article
Biochemistry & Molecular Biology
Ren-Lei Ji, Ting Liu, Zhi-Shuai Hou, Hai-Shen Wen, Ya-Xiong Tao
Summary: Four mc4r genes were identified in rainbow trout, which are homologous to those of other fish and mammals. These genes have undergone different evolutionary processes. This study provides the foundation for future research on the physiological functions of mc4r paralogs and the evolution of mc4r in vertebrates.
Editorial Material
Multidisciplinary Sciences
Chao Zhang, Ya-Xiong Tao
Article
Chemistry, Medicinal
Kenneth A. Gruber, Ren-Lai Ji, Fabio Gallazzi, Shaokai Jiang, Steven R. Van Doren, Ya-Xiong Tao, Jessica Newton Northup
Summary: During the development of a drug for treating cachexia, we discovered the importance of peptide transport across the blood-brain barrier. Through screening the medical literature, we found that bile salt transport peptides could effectively cross the BBB. We designed a drug peptide, TCMCB07, and made modifications to its C-terminal amino acid sequence to extend its half-life, providing a platform approach for producing similar drug peptides.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2022)