Review
Cell Biology
Jennifer M. Kunselman, Joshua Lott, Manojkumar A. Puthenveedu
Summary: The trafficking of GPCRs to different membrane compartments plays a critical role in their signaling profiles. Despite the similarities in structure and function, individual GPCRs are selectively regulated in their trafficking mechanisms. Recent studies have investigated the selective mechanisms involved in the endocytic and biosynthetic trafficking of GPCRs.
CURRENT OPINION IN CELL BIOLOGY
(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)
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
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
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)
Review
Biochemistry & Molecular Biology
Andreas Bock, Marcel Bermudez
Summary: Bias agonism in GPCRs is likely a result of preferential allosteric coupling from the ligand binding pocket to a specific transducer, leading to selective activation of desired signaling pathways and potentially reducing side effects.
Article
Biochemistry & Molecular Biology
Melissa Girard, Steve Dagenais Bellefeuille, Emilie Eiselt, Guillaume Arguin, Jean-Michel Longpre, Philippe Sarret, Fernand-Pierre Gendron
Summary: This study found that endosomal trafficking plays an important role in G protein-coupled receptor (GPCR) signaling. UDP selectively activates GPCR P2Y6 as a signaling molecule. The study found that MRS2693 and UDP have different effects on the internalization of the P2Y6 receptor, with MRS2693 inducing P2Y6 internalization through an independent caveolin-dependent mechanism. This study provides insights for the development of bias ligands that can influence P2Y6 signaling.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2023)
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
Malarvizhi Gurusamy, Denise Tischner, Jingchen Shao, Stephan Klatt, Sven Zukunft, Remy Bonnavion, Stefan Guenther, Kai Siebenbrodt, Roxane-Isabelle Kestner, Tanja Kuhlmann, Ingrid Fleming, Stefan Offermanns, Nina Wettschureck
Summary: The G-protein-coupled receptor P2Y10, expressed in CD4 T cells, mediates RhoA activation and migration in response to lysophosphatidylserine and ATP, which are induced in T cells upon chemokine stimulation through an autocrine/paracrine loop.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Udeep Chawla, Suchithranga M. D. C. Perera, Steven D. E. Fried, Anna R. Eitel, Blake Mertz, Nipuna Weerasinghe, Michael C. Pitman, Andrey V. Struts, Michael F. Brown
Summary: Visual rhodopsin absorbs light and takes in approximately 80 water molecules to form a solvent-swollen active state, which is essential for activating the photoreceptor and is supported by molecular dynamics simulations. Force-based measurements show that the expansion of rhodopsin occurs through changes in cavity volumes and increased hydration in the active Meta II state. Furthermore, the binding and release of the C-terminal helix of transducin is coupled to hydration changes, potentially influencing visual signal amplification through a dynamic allosteric mechanism involving lipid and water interactions in the catalytic G-protein cycle.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
James Geiger, Rick Sexton, Zina Al-Sahouri, Ming-Yue Lee, Eugene Chun, Kaleeckal G. Harikumar, Laurence J. Miller, Oliver Beckstein, Wei Liu
Summary: This study investigates the modulation of GPCRs by cholesterol through simulations and analysis, revealing specific interactions between cholesterol and beta(2)AR, as well as differential cholesterol binding in the CCK receptor subfamily. The findings contribute to a better understanding of receptor-cholesterol interactions and may lead to the development of novel therapeutics for various diseases.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
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
Pharmacology & Pharmacy
Sara T. Granados, Ramon Latorre, Yolima P. Torres
Summary: BK channels are composed of alpha and beta subunits, with changes in membrane cholesterol content affecting channel activation and the modulatory effect of E2 on channel activity.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Stefanie Kampen, Duc Duy Vo, Xiaoqun Zhang, Nicolas Panel, Yunting Yang, Mariama Jaiteh, Pierre Matricon, Per Svenningsson, Jose Brea, Maria Isabel Loza, Jan Kihlberg, Jens Carlsson
Summary: This study presents a structure-based strategy to design compounds with dual-target properties, which can both antagonize the A(2A) adenosine receptor and activate the D-2 dopamine receptor, showing promising potential as anti-parkinson drugs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Medicinal
Rina Kwag, Jieon Lee, Doyoung Kim, Haeun Lee, Miyoung Yeom, Jiwan Woo, Yakdol Cho, Hak Joong Kim, Jeongjin Kim, Gyochang Keum, Byungsun Jeon, Hyunah Choo
Summary: By designing and synthesizing a series of compounds and evaluating their activities and selectivities, it was found that one compound showed good binding affinity and selectivity for 5-HT7R, exhibiting a G protein-biased antagonistic effect. The compound demonstrated inhibitory effects on self-grooming behavior in transgenic mice, indicating that 5-HT7R may be a potential therapeutic target for treating stereotypical behaviors in autism spectrum disorder.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Meeting Abstract
Biochemistry & Molecular Biology
Alessio Accardi, Maria Falzone, Byoung-Cheol Lee, Xiaolu Cheng, George Khelashvili, Harel Weinstein
Meeting Abstract
Biochemistry & Molecular Biology
Shana Bergman, Asghar Razavi, George Khelashvili, Harel Weinstein
Article
Biochemistry & Molecular Biology
Yun Huang, Xiaoyu Wang, Guohua Lv, Asghar M. Razavi, Gerard H. M. Huysmans, Harel Weinstein, Clay Bracken, David Eliezer, Olga Boudker
NATURE CHEMICAL BIOLOGY
(2020)
Correction
Biochemical Research Methods
Ismael Rodriguez-Espigares, Mariona Torrens-Fontanals, Johanna K. S. Tiemann, David Aranda-Garcia, Juan Manuel Ramirez-Anguita, Tomasz Maciej Stepniewski, Nathalie Worp, Alejandro Varela-Rial, Adrian Morales-Pastor, Brian Medel-Lacruz, Gaspar Pandy-Szekeres, Eduardo Mayol, Toni Giorgino, Jens Carlsson, Xavier Deupi, Slawomir Filipek, Marta Filizola, Jose Carlos Gomez-Tamayo, Angel Gonzalez, Hugo Gutierrez-de-Teran, Mireia Jimenez-Roses, Willem Jespers, Jon Kapla, George Khelashvili, Peter Kolb, Dorota Latek, Maria Marti-Solano, Pierre Matricon, Minos-Timotheos Matsoukas, Przemyslaw Miszta, Mireia Olivella, Laura Perez-Benito, Davide Provasi, Santiago Rios, Ivan R. Torrecillas, Jessica Sallander, Agnieszka Sztyler, Silvana Vasile, Harel Weinstein, Ulrich Zachariae, Peter W. Hildebrand, Gianni De Fabritiis, Ferran Sanz, David E. Gloriam, Arnau Cordomi, Ramon Guixa-Gonzalez, Jana Selent
Article
Biochemical Research Methods
Ismael Rodriguez-Espigares, Mariona Torrens-Fontanals, Johanna K. S. Tiemann, David Aranda-Garcia, Juan Manuel Ramirez-Anguita, Tomasz Maciej Stepniewski, Nathalie Worp, Alejandro Varela-Rial, Adrian Morales-Pastor, Brian Medel-Lacruz, Gaspar Pandy-Szekeres, Eduardo Mayol, Toni Giorgino, Jens Carlsson, Xavier Deupi, Slawomir Filipek, Marta Filizola, Jose Carlos Gomez-Tamayo, Angel Gonzalez, Hugo Gutierrez-de-Teran, Mireia Jimenez-Roses, Willem Jespers, Jon Kapla, George Khelashvili, Peter Kolb, Dorota Latek, Maria Marti-Solano, Pierre Matricon, Minos-Timotheos Matsoukas, Przemyslaw Miszta, Mireia Olivella, Laura Perez-Benito, Davide Provasi, Santiago Rios, Ivan R. Torrecillas, Jessica Sallander, Agnieszka Sztyler, Silvana Vasile, Harel Weinstein, Ulrich Zachariae, Peter W. Hildebrand, Gianni De Fabritiis, Ferran Sanz, David E. Gloriam, Arnau Cordomi, Ramon Guixa-Gonzalez, Jana Selent
Article
Computer Science, Interdisciplinary Applications
Tu Mai Anh Do, Loic Pottier, Silvina Caino-Lores, Rafael Ferreira da Silva, Michel A. Cuendet, Harel Weinstein, Trilce Estrada, Michela Taufer, Ewa Deelman
Summary: Performance evaluation is crucial for understanding the behavior of scientific workflows, especially in dealing with in situ workflows. By proposing a lightweight metric, the resource usage efficiency of in situ workflow execution can be assessed, analyzing the tradeoffs of various configurable parameters and evaluating different execution scenarios.
JOURNAL OF COMPUTATIONAL SCIENCE
(2021)
Article
Biophysics
George Khelashvili, Ambrose Plante, Milka Doktorova, Harel Weinstein
Summary: Studies have shown that the fusion peptide (FP) of coronaviruses requires binding of Ca2+ ions to enhance penetration, but the mechanisms of membrane insertion and destabilization remain unclear.
BIOPHYSICAL JOURNAL
(2021)
Article
Biochemical Research Methods
Hector Carrillo-Cabada, Jeremy Benson, Asghar M. Razavi, Brianna Mulligan, Michel A. Cuendet, Harel Weinstein, Michela Taufer, Trilce Estrada
Summary: To successfully predict a protein's function, techniques that maintain its 3D information while performing at scale are necessary. Researchers extended a protein representation and neural network architecture, demonstrating applicability in protein function prediction and detection of conformational changes in protein trajectories.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Ambrose Plante, Harel Weinstein
Summary: Molecular Dynamics (MD) simulations are vital tools for ligand discovery and design, but the challenges of handling large datasets and rare events in complex molecular machines remain. A protocol called Rare Event Detection (RED) has been developed to efficiently detect functionally relevant responses to ligand binding, offering new insights into drug activity.
Article
Multidisciplinary Sciences
George R. Heath, Ekaterina Kots, Janice L. Robertson, Shifra Lansky, George Khelashvili, Harel Weinstein, Simon Scheuring
Summary: This study introduces a new technique called localization AFM (LAFM) that overcomes traditional AFM resolution limits by applying localization image reconstruction algorithms, allowing for structural analysis of biomolecules at the single-molecule level.
Meeting Abstract
Biophysics
George Khelashvili, Harel Weinstein
BIOPHYSICAL JOURNAL
(2021)
Meeting Abstract
Biophysics
Ekaterina Kots, Harel Weinstein
BIOPHYSICAL JOURNAL
(2021)
Meeting Abstract
Biophysics
Ekaterina D. Kots, Derek M. Shore, Harel Weinstein
BIOPHYSICAL JOURNAL
(2021)
Meeting Abstract
Biophysics
Ambrose Plante, Harel Weinstein
BIOPHYSICAL JOURNAL
(2021)
Meeting Abstract
Pathology
A. Sboner, A. Sigaras, J. Davis, S. Roshal, D. Wilkes, C. Hebding, D. Bockelman, T. Kane, S. Ackermann, M. Sigouros, J. Catalano, M. Martin, W. Song, J. Mosquera, C. Sternberg, M. Loda, H. Weinstein, O. Elemento
JOURNAL OF MOLECULAR DIAGNOSTICS
(2020)