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)
Review
Endocrinology & Metabolism
Siyuan Shen, Chang Zhao, Chao Wu, Suyue Sun, Ziyan Li, Wei Yan, Zhenhua Shao
Summary: GPCRs, as the largest family of transmembrane proteins, regulate various physiological processes. However, their complicated signal transduction pathways and difficulties in drug development have presented challenges. By identifying new ligands that bind to allosteric sites, safer drugs for treating various diseases can be designed.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemical Research Methods
Ali Isbilir, Robert Serfling, Jan Moeller, Romy Thomas, Chiara De Faveri, Ulrike Zabel, Marco Scarselli, Annette G. Beck-Sickinger, Andreas Bock, Irene Coin, Martin J. Lohse, Paolo Annibale
Summary: Fluorescence imaging methods are becoming an effective tool for quantifying membrane protein oligomerization, with a detailed protocol provided here for determining the number and oligomerization state of fluorescently labeled GPCRs. The protocol includes steps for flexible labeling strategies, image acquisition on a confocal microscope, and data analysis, allowing for application to diverse classes of membrane proteins of interest.
Review
Biochemistry & Molecular Biology
Krzysztof Jozwiak, Anita Plazinska
Summary: Studies on different receptors belonging to class A of GPCRs reveal specific molecular mechanisms behind ligand directed signaling, including the role of important residues, the impact of ligand structural features on signaling, and the key interactions between ligands and receptors.
Review
Pharmacology & Pharmacy
Hsin-Yung Yen, Ali Jazayeri, Carol Robinson
Summary: GPCRs are important drug targets due to their involvement in physiological processes. Mass spectrometry techniques, such as HDX-MS and native-MS, provide opportunities to investigate GPCR pharmacology and discover new drugs. This review highlights the potential of MS techniques for in-depth investigations of GPCR biology.
PHARMACOLOGICAL REVIEWS
(2023)
Review
Chemistry, Medicinal
Joshua W. Conner, Daniel P. Poole, Manuela Jorg, Nicholas A. Veldhuis
Summary: This review addresses the key challenges, synthesis approaches, and structure-activity relationships in recent fluorescent small molecule studies for GPCRs, and discusses the advantages of using high-resolution GPCR structures to inform conjugation strategies.
FUTURE MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Laura Lemel, Katarzyna Niescierowicz, M. Dolores Garcia-Fernandez, Leonardo Darre, Thierry Durroux, Marta Busnelli, Mylene Pezet, Fabrice Rebeille, Juliette Jouhet, Bernard Mouillac, Carmen Domene, Bice Chini, Vadim Cherezov, Christophe J. Moreau
Summary: The study revealed a stable binding of cholesterol molecules to OXTR in the presence of orthosteric ligands, leading to a positive cross-regulation between cholesterol and orthosteric ligands, which preserves the activity of the receptor in cholesterol-depleted membranes.
JOURNAL OF LIPID RESEARCH
(2021)
Review
Immunology
Jianan Zhao, Kai Wei, Ping Jiang, Cen Chang, Lingxia Xu, Linshuai Xu, Yiming Shi, Shicheng Guo, Dongyi He
Summary: In this review, the role of G-protein-coupled receptors (GPCRs) in the mechanisms of rheumatoid arthritis (RA) is discussed, and the latest clinical trials on GPCR targeting are summarized, providing a theoretical basis and guidance for the development of innovative GPCR-based clinical drugs for RA.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Kelly J. Culhane, Tejas M. Gupte, Indrani Madhugiri, Chetan J. Gadgil, Sivaraj Sivaramakrishnan
Summary: This study proposes a kinetic model to simulate the interactions between hormone, G protein coupled receptor (GPCR), and G protein. Experimental validation reveals the phenomenon of GPCR priming and the temporary enhancement of GPCR ternary complex formation by allokairic effectors. This study uncovers the kinetic mechanisms of ternary complex formation and downstream signaling.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Saravanan Konda Mani, Ramesh Thiyagarajan, Olli Yli-Harja, Meenakshisundaram Kandhavelu, Akshaya Murugesan
Summary: The human GPR17 receptor acts as a biomarker for neurological diseases. Two isoforms, long and short, of GPR17 are found in human brain tissue. The structure of the long isoform has been studied, but the structure and activation mechanism of the short isoform remain unclear. In this study, the researchers modeled the structure of the short isoform and identified two distinct ligand binding sites. The binding of the endogenous ligand UDP was found to be stronger in both binding sites, suggesting its importance in the signaling and communication properties of GPR17. These findings may contribute to the development of targeted therapies for neurological diseases.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2023)
Article
Chemistry, Physical
Daria B. Kokh, Rebecca C. Wade
Summary: The study demonstrates that the tau RAMD approach is able to reproduce relative residence times and reveal dissociation mechanisms effectively, with results consistent with more computationally intensive simulation methods. The simulations accurately predict ligand dissociation rates and changes in residence time due to allosteric modulation.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Article
Multidisciplinary Sciences
Vaithish Velazhahan, Ning Ma, Gaspar Pandy-Szekeres, Albert J. Kooistra, Yang Lee, David E. Gloriam, Nagarajan Vaidehi, Christopher G. Tate
Summary: GPCRs are divided into six classes, with structures of vertebrate GPCRs well understood but not of fungal class D GPCRs. This study reveals the structure of a class D GPCR in yeast and its coupling to G proteins, providing a template for the design of drugs to treat fungal diseases.
Article
Multidisciplinary Sciences
He Tian, Kathryn M. Gunnison, Manija A. Kazmi, Thomas P. Sakmar, Thomas Huber
Summary: In this study, Rho mutants were engineered as FRET sensors to measure the kinetics and energetics of 11CR binding using genetic code expansion and bioorthogonal labeling. The study found that mutations in the channel between transmembrane helices 5 and 6 dramatically affected 11CR binding kinetics, but not agonist release kinetics. The findings provided direct experimental evidence for the entry of 11CR between TM5/6 in Rho, involving dynamic allosteric control of the ligand entry channel. These findings proposed a conceptual framework for understanding the function of G protein-coupled receptors with hydrophobic ligands that enter their binding pockets through transmembrane pores.
Review
Biochemistry & Molecular Biology
Thian-Sze Wong, Guangzhi Li, Shiliang Li, Wei Gao, Geng Chen, Shiyi Gan, Manzhan Zhang, Honglin Li, Song Wu, Yang Du
Summary: Neuropsychiatric disorders are complex and have various causes. Finding effective treatment targets is difficult due to the heterogeneous nature of these diseases. However, the growing knowledge of G protein-coupled receptors (GPCRs) provides a potential avenue for drug discovery. Understanding the molecular mechanisms and structures of GPCRs can aid in the development of effective drugs. This review provides an overview of the role of GPCRs in neurodegenerative and psychiatric diseases, highlights new opportunities for GPCR targets, and discusses recent progress in GPCR drug development.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Review
Biochemistry & Molecular Biology
Wolfgang Sadee
Summary: G-protein-coupled receptors (GPCRs) are versatile sensors and regulators of cellular functions, existing in complex aggregates with multiple conformations. They can detect weak stimuli and activate spontaneously, resulting in basal ligand-free signaling. Agonists trigger a cascade of events leading to an activated agonist-receptor G-protein complex, but the signaling process can remodel the receptor complex and reduce agonist affinity, causing ligand dissociation. Continued stimulation can regulate sustained ligand-free signaling, and this review focuses on opioid and serotonin receptors, and the growth hormone secretagogue receptor (GHSR), proposing the hypothesis that ligand-free signaling of 5-HT2A receptors mediates the therapeutic effects of psychedelic drugs. Research avenues are suggested to enhance our understanding of ligand-free GPCR signaling.
Article
Biochemistry & Molecular Biology
Dursun Nizam Korkut, Isabel D. Alves, Alexander Vogel, Sandrine Chabas, Cynthia M. Sharma, Denis Martinez, Antoine Loquet, Gilmar F. Salgado, Fabien Darfeuille
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2020)
Article
Biochemistry & Molecular Biology
Astrid Walrant, Antonio Bauza, Claudia Girardet, Isabel D. Alves, Sophie Lecomte, Francoise Illien, Sebastien Cardon, Natpasit Chaianantakul, Manjula Pallerla, Fabienne Burlina, Antonio Frontera, Sandrine Sagan
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2020)
Article
Biochemistry & Molecular Biology
Pierre Calmet, Christophe Cullin, Sandra Cortes, Maylou Vang, Nada Caudy, Rim Baccouch, Jean Dessolin, Nada Taib Maamar, Sophie Lecomte, Bruno Tillier, Isabel D. Alves
Article
Radiology, Nuclear Medicine & Medical Imaging
Adrien Chastel, Dennis J. Worm, Isabel D. Alves, Delphine Vimont, Melina Petrel, Samantha Fernandez, Philippe Garrigue, Philippe Fernandez, Elif Hindie, Annette G. Beck-Sickinger, Clement Morgat
Article
Cell Biology
Michael Trichet, Rosamaria Lappano, Mathilde Belnou, Lilian Shadai Salazar Vazquez, Isabel Alves, Delphine Ravault, Sandrine Sagan, Lucie Khemtemourian, Marcello Maggiolini, Yves Jacquot
Article
Biochemistry & Molecular Biology
Mehdi Azouz, Mathilde Gonin, Sebastian Fiedler, Jonathan Faherty, Marion Decossas, Christophe Cullin, Sandrine Villette, Michel Lafleur, Isabel D. Alves, Sophie Lecomte, Alexandre Ciaccafava
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2020)
Article
Medicine, Research & Experimental
Fabienne Soulet, Clement Bodineau, Katarzyna B. Hooks, Jean Descarpentrie, Isabel Alves, Marielle Dubreuil, Amandine Mouchard, Malaurie Eugenie, Jean-Luc Hoepffner, Jose J. Lopez, Juan A. Rosado, Isabelle Soubeyran, Mercedes Tome, Raul Duran, Macha Nikolski, Bruno O. Villoutreix, Serge Evrard, Geraldine Siegfried, Abdel-Majid Khatib
Review
Biochemistry & Molecular Biology
Estelle Rascol, Sandrine Villette, Etienne Harte, Isabel D. Alves
Summary: Plasmon waveguide resonance (PWR) is a variant of surface plasmon resonance (SPR) invented about two decades ago at the University of Arizona. PWR offers the advantage of monitoring both mass and structural changes, in addition to characterizing the kinetics and affinity of molecular interactions. It is especially useful for studying molecular interactions in anisotropic-oriented thin films.
Article
Biochemistry & Molecular Biology
Rim Baccouch, Estelle Rascol, Kaja Stoklosa, Isabel D. Alves
Summary: GPCRs are membrane proteins that sense extracellular signals and activate intracellular signaling pathways. Their structure and function are influenced by the surrounding lipid environment and membrane properties. Lipids can act as important cofactors and play a role in GPCR activity.
BIOPHYSICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Estelle Rascol, Anouk Dufourquet, Rim Baccouch, Pierre Soule, Isabel D. Alves
Summary: A novel experimental procedure using microscale thermophoresis (MST) directly from cell membrane fragments was developed to determine ligand binding affinities to membrane proteins. The procedure overcame the challenge of purification and successfully determined the concentration and binding affinity of the dopamine D2 receptor.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Rim Baccouch, Yarong Shi, Emilie Vernay, Marion Mathelie-Guinlet, Nada Taib-Maamar, Sandrine Villette, Cecile Feuillie, Estelle Rascol, Philippe Nuss, Sophie Lecomte, Michael Molinari, Galya Staneva, Isabel D. Alves
Summary: The lipid composition and balance in cellular membranes can be influenced by various factors, including aging, pathologies, and diets. In individuals with psychiatric disorders, such as schizophrenia, the cell membranes have been found to be deficient in polyunsaturated fatty acids (PUFAs), which could impact the interaction of medications and the activation of receptors embedded in the lipid membrane. Understanding how changes in PUFA levels affect membrane properties is crucial.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2023)
Article
Biochemistry & Molecular Biology
Marie-Lise Jobin, Veronique De Smedt-Peyrusse, Fabien Ducrocq, Rim Baccouch, Asma Oummadi, Maria Hauge Pedersen, Brian Medel-Lacruz, Maria-Florencia Angelo, Sandrine Villette, Pierre Van Delft, Laetitia Fouillen, Sebastien Mongrand, Jana Selent, Tarson Tolentino-Cortez, Gabriel Barreda-Gomez, Stephane Gregoire, Elodie Masson, Thierry Durroux, Jonathan A. Javitch, Ramon Guixa-Gonzalez, Isabel D. Alves, Pierre Trifilieff
Summary: Increasing evidence suggests a connection between lipid metabolism and mental health, particularly in relation to polyunsaturated fatty acids (PUFAs). Recent findings show that PUFA levels in the brain are linked to dopamine transmission, a key system involved in psychiatric symptoms. However, the underlying mechanisms of this relationship are still unclear.
MOLECULAR PSYCHIATRY
(2023)
Meeting Abstract
Biophysics
Rim Baccouch, Verronique de Smedt-Peyrusse, Marie-Lise Jobin, Thierry Durroux, David Perrais, Pierre Trifilieff, Isabel D. Alves
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2021)
Article
Biochemical Research Methods
Isabel D. Alves
BIOPHYSICS OF MEMBRANE PROTEINS: Methods and Protocols
(2020)
Article
Multidisciplinary Sciences
Jian-Qiao Jiang, Christel Chanseau, Isabel D. Alves, Sylvain Nlate, Marie-Christine Durrieu
Article
Medicine, Research & Experimental
Yuwen Zhu, Yan Guo, Yujia Xue, Anqi Zhou, Ying Chen, Yifei Chen, Xiulian Miao, Fangqiao Lv
Summary: BRG1 plays an important role in HSC-myofibroblast transition and targeting it could be a reasonable strategy for liver fibrosis intervention.
Article
Medicine, Research & Experimental
Liu Ye, Beibei Liu, Jingling Huang, Xiaolin Zhao, Yuan Wang, Yungen Xu, Shuping Wang
Summary: Doublecortin-like kinase 1 (DCLK1) is a significant prooncogenic factor that is strongly associated with the malignant progression and clinical prognosis of various cancers. DCLK1 plays important roles in stem cell marker regulation, tumor cell reprogramming, and immune evasion. However, the exact biological functions of DCLK1, especially the disparities between its alpha- and beta-form transcripts in cancer progression, remain ambiguous.
Article
Medicine, Research & Experimental
Jiahui Yang, Xiaoyu Chen, Tianjing Liu, Yongyan Shi
Summary: This article reviews the role of bile acids in necrotizing enterocolitis (NEC) and their potential therapeutic value. The dysregulation of bile acids is associated with intestinal injury, and inflammatory factors in the liver also play a crucial role in regulating bile acid transport. The bile acid metabolic pathway is important for regulating intestinal microbiota, cell proliferation, and barrier protection.
Review
Medicine, Research & Experimental
Zhenzheng Zhu, Yuemiao Xu, Yuwei Xia, Xinru Jia, Yixin Chen, Yuyue Liu, Leyin Zhang, Hui Chai, Leitao Sun
Summary: Bile acid, as the final product of cholesterol breakdown, plays a complex regulatory and signaling role in human metabolism. Research suggests that it has the potential to enhance metabolism and regulate chronic metabolic diseases through various pathways. The interaction between bile acid and gut microbiota is also of great significance.
Article
Medicine, Research & Experimental
Xin He, Hong-Xu Zhou, Xian Fu, Kai-Di Ni, Ai-Zhi Lin, Ling-Tong Zhang, Hou-Hua Yin, Qing Jiang, Xue Zhou, Yi-Wen Meng, Jun-Yan Liu
Summary: DON exposure causes an increase in deoxycholic acid (DCA), which contributes to intestinal injury. DCA may be a potential therapeutic target for DON enterotoxicity.
Article
Medicine, Research & Experimental
Zhitao Wang, Heng Ma, Abdul Nasir, Sufang Liu, Zhisong Li, Feng Tao, Qian Bai
Summary: This study reveals the involvement of TET1-mediated epigenetic regulation in chronic TMJ pain through trigeminal TNF alpha signaling.
Article
Medicine, Research & Experimental
Lu Yu, Hao Ran, Yaru Lu, Qian Ma, Huan Huang, Weibin Liu
Summary: This study found that the HIF-1 alpha inhibitor BAY 87-2243 can alleviate the symptoms of the Experimental Autoimmune Myasthenia Gravis (EAMG) inflammation model. BAY 87-2243 can restore the balance of CD4(+)T cell subsets, reduce the production of pro-inflammatory cytokines, and act as both an immune imbalance regulator and anti-inflammatory.
Article
Medicine, Research & Experimental
Alex Peralvarez-Marin, Montse Sole, Judith Serrano, Alice Taddeucci, Belen Perez, Clara Penas, Gemma Manich, Marcel Jimenez, Pilar D'Ocon, Francesc Jimenez-Altayo
Summary: This study provides the first evidence that TRPV2 channels may modulate vascular tone by balancing opposing inputs from the endothelium and smooth muscle, leading to net vasodilation. The amplification of TRPV2 channel-induced activity by NO emphasizes the pathophysiological relevance of these findings.
Article
Medicine, Research & Experimental
Amin Ullah, Jing Zhao, Jiakun Li, Rajeev K. Singla, Bairong Shen
Summary: Gastric cancer is the fifth-most prevalent and second-most deadly cancer worldwide. Late onset of symptoms makes early detection important. CXC chemokines play an important role in the pathological process of gastric cancer, but their exact role in diagnosis and prognosis is not fully understood. Inhibiting CXC chemokines shows promise as a targeted therapy.
Article
Medicine, Research & Experimental
Menna S. Zeyada, Salma M. Eraky, Mamdouh M. El-Shishtawy
Summary: The current study demonstrates the prophylactic and antifibrotic effects of Trig against BLM-induced PF by targeting multiple signaling pathways. The combination of Trig and Pirf may be a promising approach to enhance Pirf's anti-fibrotic effect.