Review
Biochemistry & Molecular Biology
Shafi Ullah Khan, Nafees Ahemad, Lay-Hong Chuah, Rakesh Naidu, Thet Thet Htar
Summary: G protein-coupled receptors (GPCRs) are the largest family of protein targets, with at least 500 members being therapeutic targets. G protein-coupled estrogen receptor-1 (GPER-1) has the ability in estrogen signaling and is considered a potential therapeutic target for estrogen-based cancers and other non-communicable diseases. However, the progress in understanding the structure and function of GPER-1 has been slow due to the limited availability of selective GPER-1 modulators.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Review
Biochemistry & Molecular Biology
Preethi C. Karnam, Sergey A. Vishnivetskiy, Vsevolod V. Gurevich
Summary: Arrestins are a small family of proteins that bind G protein-coupled receptors (GPCRs) with high affinity to active phosphorylated GPCRs. They must have two sensors, which detect receptor-attached phosphates and the active receptor conformation independently, enabling transition into a high-affinity receptor-binding state. This transition involves a global conformational rearrangement that stabilizes the complex by bringing additional elements of the arrestin molecule in contact with a GPCR.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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
Cardiac & Cardiovascular Systems
Yuanqiang Li, Boyu Li, Wei-Dong Chen, Yan-Dong Wang
Summary: Cardiovascular diseases (CVDs) are the leading cause of death globally, accounting for nearly 30% of deaths worldwide annually. G-protein-coupled receptors (GPCRs) are vital in regulating cellular physiology and pathology, and play a crucial role in CVDs. Targeting GPCRs has become an important approach for the treatment of CVDs, with some GPCR antagonists serving as standard therapy.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Jeremie Topin, Cedric Bouysset, Jody Pacalon, Yiseul Kim, Mee-Ra Rhyu, Sebastien Fiorucci, Jerome Golebiowski
Summary: Bitter taste receptors (TAS2Rs) are a poorly understood subgroup of G protein-coupled receptors (GPCRs), with their experimental structure yet to be determined and key-residues controlling their function mostly unknown. Researchers designed an integrative approach to improve comparative modeling of TAS2Rs.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Mohammad Zulqurnain Haider, Amirhossein Sahebkar, Ali H. Eid
Summary: Atherosclerosis is a major cause of cardiovascular disease-related morbidity and mortality, with higher mortality rates in men than women. It has been suggested that estrogen plays a protective role in the cardiovascular system through the membranous G-protein coupled estrogen receptor, GPER1. Activation of GPER1 regulates vascular smooth cell phenotype and reduces LDL levels by promoting LDL receptor expression and facilitating LDL re-uptake in liver cells. Selective activation of GPER1 may be a promising strategy to prevent or suppress atherosclerosis with fewer side effects compared to non-selective estrogen.
CURRENT MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Qiuyan Chen, Manolo Plasencia, Zhuang Li, Somnath Mukherjee, Dhabaleswar Patra, Chun-Liang Chen, Thomas Klose, Xin-Qiu Yao, Anthony A. Kossiakoff, Leifu Chang, Philip C. Andrews, John J. G. Tesmer
Summary: GRKs selectively phosphorylate activated GPCRs for desensitization, with a conserved region at the GRK N terminus playing a crucial role. Cryo-EM reconstructions revealed the binding mechanism between GRK1 and Rho*, providing insights into how a small family of protein kinases can recognize and be activated by numerous GPCRs.
Article
Multidisciplinary Sciences
Li-Hua Zhao, Jingyu Lin, Su-Yu Ji, X. Edward Zhou, Chunyou Mao, Dan-Dan Shen, Xinheng He, Peng Xiao, Jinpeng Sun, Karsten Melcher, Yan Zhang, Xiao Yu, H. Eric Xu
Summary: This study presents the structures of CRF2R bound to UCN1 and coupled to G proteins G(11) and G(o), and compares them with the structure of CRF2R bound to G(s), uncovering the structural differences that determine the selective coupling of G protein subtypes by CRF2R.
NATURE COMMUNICATIONS
(2022)
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
Pharmacology & Pharmacy
Torsten Schoeneberg, Ines Liebscher
Summary: GPCR genes play key roles in the human genome, participating in various physiological functions and serving as important therapeutic targets. In addition to classical mutations, various aspects contribute to the complexity of GPCR dysfunctions. With the emergence of new technologies, further research and therapeutic approaches are expected to be explored.
PHARMACOLOGICAL REVIEWS
(2021)
Article
Polymer Science
Zhe Fu, Linjie Zhang, Sijin Hang, Shiyi Wang, Na Li, Xiaojing Sun, Zian Wang, Ruilong Sheng, Fang Wang, Wenhui Wu, Ruihua Guo
Summary: In this study, a series of coumarin derivatives were synthesized and evaluated for their GPCR activation or inhibitory activities. Some of the compounds showed remarkable GPCR activation or inhibitory potency, and the conversion of activators to inhibitors was successfully achieved by specific chemical modifications. This work provides a simple and efficient approach for developing coumarin derivatives as GPCR activators and inhibitors with potential applications in disease treatment.
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
Biology
Ke An, Xiaohong Zhu, Chen Bai
Summary: This study investigates the relationship between the 3D structures and activation mechanisms and functions of G-protein-coupled receptors (GPCRs). By calculating the activation free-energy landscapes, a consistent picture of the activation mechanisms between different types of GPCRs is obtained.
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.
Article
Chemistry, Medicinal
Francesco Raimondi, Angelo Feline, Francesca Fanelli
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2015)
Review
Biochemistry & Molecular Biology
Francesca Fanelli, Angelo Felline, Francesco Raimondi, Michele Seeber
BIOCHEMICAL SOCIETY TRANSACTIONS
(2016)
Article
Chemistry, Physical
Angelo Feline, Simona Mariani, Francesco Raimondi, Luca Bellucci, Francesca Fanelli
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2017)
Article
Multidisciplinary Sciences
Jonathan Zapata, Edoardo Moretto, Saad Hannan, Luca Murru, Anna Longatti, Davide Mazza, Lorena Benedetti, Matteo Fossati, Christopher Heise, Luisa Ponzoni, Pamela Valnegri, Daniela Braida, Mariaelvina Sala, Maura Francolini, Jeffrey Hildebrand, Vera Kalscheuer, Francesca Fanelli, Carlo Sala, Bernhard Bettler, Silvia Bassani, Trevor G. Smart, Maria Passafaro
NATURE COMMUNICATIONS
(2017)
Review
Pharmacology & Pharmacy
Pier G. De Benedetti, Francesca Fanelli
DRUG DISCOVERY TODAY
(2018)
Article
Biochemical Research Methods
Michele Seeber, Angelo Felline, Francesco Raimondi, Simona Mariani, Francesca Fanelli
Article
Biochemistry & Molecular Biology
Kim C. Jonas, Francesca Fanelli, Ilpo T. Huhtaniemi, Aylin C. Hanyaloglu
JOURNAL OF BIOLOGICAL CHEMISTRY
(2015)
Article
Multidisciplinary Sciences
Hoi Ling Luk, Nihar Bhattacharyya, Fabio Montisci, James M. Morrow, Federico Melaccio, Akimori Wada, Mudi Sheves, Francesca Fanelli, Belinda S. W. Chang, Massimo Olivucci
SCIENTIFIC REPORTS
(2016)
Article
Biochemistry & Molecular Biology
Advait Subramanian, Anita Capalbo, Namrata Ravi Iyengar, Riccardo Rizzo, Antonella di Campli, Rosaria Di Martino, Matteo Lo Monte, Andrea R. Beccari, Amol Yerudkar, Carmen del Vecchio, Luigi Glielmo, Gabriele Turacchio, Marinella Pirozzi, Sang Geon Kim, Petra Henklein, Jorge Cancino, Seetharaman Parashuraman, Dario Diviani, Francesca Fanelli, Michele Sallese, Alberto Luini
Article
Chemistry, Physical
Laura Pedraza-Gonzalez, Luca De Vico, Maria del Carmen Marin, Francesca Fanelli, Massimo Olivucci
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2019)
Article
Neurosciences
Fiammetta Monacelli, Lucia Martella, Maria Nives Parodi, Patrizio Odetti, Francesca Fanelli, Massimo Tabaton
JOURNAL OF ALZHEIMERS DISEASE
(2019)
Article
Chemistry, Medicinal
Angelo Felline, Luca Belmonte, Francesco Raimondi, Luca Bellucci, Francesca Fanelli
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2019)
Article
Biochemistry & Molecular Biology
Angelo Felline, Michela Ghitti, Giovanna Musco, Francesca Fanelli
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2017)
Article
Biochemistry & Molecular Biology
Dario Diviani, Francesco Raimondi, Cosmo D. Del Vescovo, Elisa Dreyer, Erica Reggi, Halima Osman, Lucia Ruggieri, Cynthia Gonano, Sabrina Cavin, Clare L. Box, Marc Lenoir, Michael Overduin, Luca Bellucci, Michele Seeber, Francesca Fanelli
CELL CHEMICAL BIOLOGY
(2016)
Article
Multidisciplinary Sciences
Petra Behnen, Angelo Felline, Antonella Comitato, Maria Teresa Di Salvo, Francesco Raimondi, Sahil Gulati, Shirin Kahremany, Krzysztof Palczewski, Valeria Marigo, Francesca Fanelli
