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
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
Biochemistry & Molecular Biology
Alfredo Ulloa-Aguirre, Teresa Zarinan, Eduardo Jardon-Valadez
Summary: This review discusses the mechanisms by which mutations in GPCRs involved in endocrine function in humans lead to misfolding, decreased plasma membrane expression of the receptor protein, and loss-of-function diseases. Special attention is given to misfolded GPCRs that regulate reproductive function, and promising therapeutic interventions targeting trafficking of these defective proteins to rescue their normal function are also described.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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)
Review
Chemistry, Multidisciplinary
Bingjie Zhang, Shanshan Li, Wenqing Shui
Summary: G protein-coupled receptors (GPCRs) are a large family of proteins that play significant roles in cellular and physiological responses. Post-translational modifications (PTMs) of GPCRs, such as glycosylation, phosphorylation, ubiquitination and palmitoylation, have important regulatory functions in receptor folding, biosynthesis, trafficking, dimerization and signaling. This review provides an overview of PTMs in GPCRs, focusing on their types, locations, cross talk and dynamic regulation, which can shed light on the molecular basis of GPCRs and contribute to structure-based drug discovery.
FRONTIERS IN CHEMISTRY
(2022)
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
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)
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.
Review
Engineering, Biomedical
Yuhong Jiang, Yuke Li, Xiujuan Fu, Yue Wu, Rujing Wang, Mengnan Zhao, Canquan Mao, Sanjun Shi
Summary: The translation article introduces the interaction between G protein-coupled receptors (GPCRs) and nanotechnology, as well as how nanotechnology can improve the efficacy and safety of GPCR-related drugs. Nanotechnology can encapsulate GPCR ligands to construct synthetic nano-GPCRs and precisely initiate sustained endosomal signal transduction through nanoparticles. Moreover, nanoparticles can enhance the potency of delivery systems by actively targeting specific cells through ligand-receptor binding and receptor-dependent endocytosis.
ACTA BIOMATERIALIA
(2023)
Review
Pharmacology & Pharmacy
Xiaoqing Guo, Qin Li, Shulan Pi, Yuanpeng Xia, Ling Mao
Summary: P2Y receptors are a critical group of G protein-coupled receptors that signal through dimers, playing diverse roles in physiology and pathology. Research has shown the significance of dimerization between P2Y receptors and other receptors in cardiovascular and cerebrovascular processes.
BIOCHEMICAL PHARMACOLOGY
(2021)
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
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
Chien Lee, Bo-Han Su, Yufeng Jane Tseng
Summary: Neural network-based protein modeling methods have made significant progress in recent years. This study compares the performance of these methods with the widely used template-based software Modeller in G-protein-coupled receptor (GPCR) protein modeling. The results show that, in cases where no good templates are available, the neural network-based methods outperformed the template-based method.
BRIEFINGS IN BIOINFORMATICS
(2022)
Review
Cardiac & Cardiovascular Systems
Alyssa Grogan, Emilio Y. Lucero, Haoran Jiang, Howard A. Rockman
Summary: G protein-coupled receptors (GPCRs) play key roles in cardiac health and disease, and are targeted for the treatment of cardiovascular diseases. Recent advancements in understanding GPCR signaling, regulation, and pharmacological properties have provided valuable insights.
CARDIOVASCULAR RESEARCH
(2023)
Article
Oncology
Theodoros Michelakos, Lei Cai, Vincenzo Villani, Francesco Sabbatino, Filippos Kontos, Carlos Fernandez-del Castillo, Teppei Yamada, Azfar Neyaz, Martin S. Taylor, Vikram Deshpande, Tomohiro Kurokawa, David T. Ting, Motaz Qadan, Colin D. Weekes, Jill N. Allen, Jeffrey W. Clark, Theodore S. Hong, David P. Ryan, Jennifer Y. Wo, Andrew L. Warshaw, Keith D. Lillemoe, Soldano Ferrone, Cristina R. Ferrone
Summary: This study evaluated the immune response induced by neoadjuvant therapy in PDAC patients. The findings suggest that neoadjuvant FOLFIRINOX may lead to immunologically relevant changes in the tumor microenvironment, reducing HLAA defects, increasing CD8(+) cell density, and decreasing T regulatory cell and M2 macrophage density.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2021)
Article
Cell Biology
Yin P. Hung, Athena L. Chen, Martin S. Taylor, Tiffany G. Huynh, Marina Kem, Martin K. Selig, G. Petur Nielsen, Jochen K. Lennerz, Christopher G. Azzoli, Ibiayi Dagogo-Jack, Richard L. Kradin, Mari Mino-Kenudson
Summary: Thoracic NUT carcinoma, driven by NUTM1 rearrangements, can rarely express TTF-1 and/or multiple neuroendocrine markers, leading to diagnostic confusion with other tumor types. NUT immunohistochemistry and/or NUTM1 molecular testing should be considered in primitive-appearing tumors to avoid misdiagnosis.
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)
Letter
Critical Care Medicine
Jenna O. Miller, Angela R. Shih, Mari Mino-Kenudson, Martin S. Taylor, Jennifer L. Goldman
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(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
Radiology, Nuclear Medicine & Medical Imaging
Mark A. Anderson, Ranjodh S. Dhami, Colin M. Fadzen, George Molina, Martin S. Taylor, Vikram Deshpande, Motaz Qadan, Onofrio A. Catalano, Cristina R. Ferrone, Amirkasra Mojtahed
Summary: CT and MRI features can accurately differentiate MCNs from simple liver cysts, with thick septations/nodularity, biliary dilation, thin septations, internal hemorrhage/debris, perfusional change, and fewer than 3 coexistent liver cysts being features that help differentiate MCNs. MRI has advantages over CT in detecting these features.
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.
Article
Oncology
Steffen Rickelt, Azfar Neyaz, Charlene Condon, Charles A. Whittaker, Ali H. Zaidi, Martin S. Taylor, Genevieve Abbruzzese, Anthony R. Mattia, Lawrence Zukerberg, Stuti G. Shroff, Omer H. Yilmaz, Osman Yilmaz, Elizabeth Y. Wu, Won-Tak Choi, Blair A. Jobe, Robert D. Odze, Deepa T. Patil, Vikram Deshpande, Richard O. Hynes
Summary: The study reveals changes in extracellular matrix (ECM) during the progression of Barrett's esophagus-related neoplasia. Loss of BM AGRN is identified as a novel diagnostic biomarker that can identify NDBE patients at increased risk of developing advanced neoplasia.
CLINICAL CANCER RESEARCH
(2022)
Letter
Gastroenterology & Hepatology
Minyi Lee, George Eng, Anna Handte-reinecker, Vikram S. Deshpande, Omer H. Yilmaz, Manish K. Gala
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)