Article
Biochemistry & Molecular Biology
Kwabena Owusu Dankwah, Jonathon E. Mohl, Khodeza Begum, Ming-Ying Leung
Summary: This study computationally predicted the binding of a single ligand to GPCRs from different families and uncovered similar binding pockets that contribute to ligand interactions. These findings can be applied to improve protein function inference, drug repurposing, drug toxicity prediction, and the acceleration of new drug development.
Article
Multidisciplinary Sciences
Benjamin Tajer, James A. Dutko, Shawn C. Little, Mary C. Mullins
Summary: The study explores the BMP2/7 heterodimer signaling mechanism in zebrafish embryos, revealing that BMP2 homodimers require nonredundant type I receptors Acvr1 and Bmpr1 for signaling, despite not being able to bind Acvr1 in vitro. The kinase activity of Acvr1 is essential for the signaling complex, suggesting that the potency of the heterodimer arises from recruiting both Acvr1 and Bmpr1.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Oanh Vu, Brian Joseph Bender, Lisa Pankewitz, Daniel Huster, Annette G. Beck-Sickinger, Jens Meiler
Summary: G protein-coupled receptors (GPCRs) are the largest membrane protein family and a significant target class for therapeutics. The class A receptors of GPCRs affect various aspects of human physiology. Many peptides that bind to these receptors undergo interaction and conformational changes.
Article
Pharmacology & Pharmacy
Leandro Ceotto Freitas-Lima, Andrea Pacesova, Jana Stanurova, Pavel Sacha, Ales Marek, Martin Hubalek, Jaroslav Kunes, Blanka Zelezna, Lenka Maletinska
Summary: The study found that GPR160 is not the receptor for CARTp, as no specific binding of CARTp was detected in PC12 cells, THP1 cells, and GPR160-transfected cells.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Immunology
Athanasios Papakyriakou, Anastasia Mpakali, Efstratios Stratikos
Summary: This study investigates the heterodimerization topology between endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2) using computational molecular dynamics calculations. The proposed model involves the exon 10 loop, suggesting a potential role and significance of ERAP1/ERAP2 molecular interactions.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Medicinal
Luying Chen, Akiharu Uwamizu, Kuniyuki Kano, Yuko Otani, Sho Kondo, Asuka Inoue, Junken Aoki, Tomohiko Ohwada
Summary: Lysophosphatidylserine (LysoPS) is an endogenous pan-agonist of three G-protein coupled receptors (GPCRs): LPS1/GPR34, LPS2/P2Y10, and LPS3/GPR174. LPS1 agonist activity is sensitive to structural changes at the hydrophobic fatty acid moiety, while LPS2 agonist activity is not. In this study, a new class of hydrophobic fatty acid surrogates with a biphenyl-ether scaffold was developed to investigate the molecular basis of LPS2 agonist binding. The putative ligand-binding site of LPS2 is Gamma-shaped and has a hydrophilic site embedded in the receptor transmembrane helix bundles and a hydrophobic groove adjoining transmembrane domains 4 and 5.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Efpraxia Tzortzini, Antonios Kolocouris
Summary: Most membrane lipids interact with GPCRs structures and modulate their function. PIP2 and cholesterol have an impact on the conformational equilibria of the A(2A) adenosine receptor.
Review
Oncology
Gyoergy Trencsenyi, Gabor Halmos, Zita Kepes
Summary: Due to the increasing prevalence of malignant diseases and related metastases, there is a need for specific diagnostic vectors that can identify tumors in a timely and selective manner. Multi-target imaging using multivalent ligands has emerged as an effective way to increase the binding ability of peptide-based molecular vectors in cancer research. The colocalization of the asparagine-glycine-arginine (NGR) motif with angiogenesis-related Aminopeptidase N (APN/CD13) makes radiolabelled NGR-containing bispecific compounds valuable tools for molecular diagnostics of APN/CD13 overexpressing tumors. The establishment of vascular-homing heterobivalent probes not only expands the horizon of cancer diagnostics but also contributes to the goal of personalized tumor imaging.
Review
Biochemistry & Molecular Biology
Kimia Kaffashi, Didier Dreau, Irina V. Nesmelova
Summary: Chemokines are signaling proteins that play a crucial role in cell-cell communication, migration, and trafficking. The oligomerization state of chemokines affects their biological activity, and heterooligomerization can significantly impact cellular responses. Recent studies on obligate heterodimers have provided valuable insights into the functional roles and molecular mechanisms of chemokine heterodimers. This review focuses on the latest progress in understanding the roles of chemokine heterodimers and their contribution to the functioning of the chemokine network.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Apeksha Parajulee, Kuglae Kim
Summary: Serotonin receptors, belonging to the GPCRs superfamily, mediate the effects of serotonin in mood regulation, cognition, and appetite. Understanding their structure, functions, and pharmacology is crucial for developing targeted therapeutics for neuropsychiatric disorders. However, the structural similarities among receptor subtypes pose challenges in developing selective drugs.
Article
Biochemistry & Molecular Biology
Attila Egyed, Adam A. Kelemen, Marton Vass, Andras Visegrady, Stephanie A. Thee, Zhiyong Wang, Chris de Graaf, Jose Brea, Maria Isabel Loza, Rob Leurs, Gyorgy M. Keseru
Summary: Recent structural studies have identified several allosteric sites for pharmacological intervention in addition to the orthosteric binding pockets of GPCRs. Through a virtual screening protocol, new bitopic compounds targeting specific receptor profiles were designed. The designed compounds showed biased selectivity towards the desired receptor targets and successfully addressed limitations of known drugs.
BIOORGANIC CHEMISTRY
(2021)
Article
Endocrinology & Metabolism
Mahvash A. Goolam, Alice P. Brown, Kimberly T. Edwards, Karen J. Gregory, Katie Leach, Arthur D. Conigrave
Summary: The calcium-sensing receptor plays a crucial role in regulating human calcium and mineral metabolism by sensing extracellular Ca2+. Mutations in the receptor can impair its function and calcium sensitivity, and receptor asymmetry may contribute to the underlying mechanisms.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
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)
Article
Pharmacology & Pharmacy
Remy Bonnavion, Shangmin Liu, Haruya Kawase, Kenneth Anthony Roquid, Stefan Offermanns
Summary: A recent study discovered that GPR182, a novel chemokine receptor expressed in microvascular and lymphatic endothelial cells, plays a crucial role in immune regulation by binding to various chemokines and regulating their distribution. The study also found that GPR182 has a strong affinity for multiple chemokines, highlighting its importance in chemokine scavenging.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Psychology, Multidisciplinary
Andrea Ghiani, Marcello Maniglia, Luca Battaglini, David Melcher, Luca Ronconi
Summary: Neurophysiological studies using MEG and EEG show that oscillatory rhythmic brain activity may be crucial for binding sensory information to generate unified perceptual representation. Modulating brain oscillations with tACS can provide insights into binding processes, with current evidence supporting the causal role of oscillatory activity in spatial, temporal, and feature binding in visual perception.
FRONTIERS IN PSYCHOLOGY
(2021)