Article
Biochemistry & Molecular Biology
Shuya Kate Huang, Louis-Philippe Picard, Rima S. M. Rahmatullah, Aditya Pandey, Ned Van Eps, Roger K. Sunahara, Oliver P. Ernst, Adnan Sljoka, R. Scott Prosser
Summary: Fluorine nuclear magnetic resonance spectroscopy was used to study the conformational equilibria of the human stimulatory G-protein alpha subunit (G(s)α) in different states. The results showed that the equilibrium is influenced by nucleotide, beta gamma subunit, lipid bilayer, and adenosine A(2A) receptor (A(2A)R). Different helices of G(s)α exhibited dynamic behavior and underwent interactions and transitions associated with G-protein activation. The study revealed a conformational landscape influenced by nucleotides, lipid bilayer, and G-protein-coupled receptor.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Masaki Saito, Ayano Chiba, Takeya Sato, Takahiro Moriya, Jun Sukegawa, Norimichi Nakahata
Summary: Proteins interacting with G protein-coupled receptors can modulate signal transduction, and in this study, Tctex-1 was found to enhance PTHR-mediated signaling by activating adenylyl cyclase. Additionally, Tctex-1 was shown to directly bind to AC type 6, revealing a novel mechanism of GPCR/G(s) signaling regulation by Tctex-1.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Leigh A. Stoddart, Laura E. Kilpatrick, Ross Corriden, Barrie Kellam, Stephen J. Briddon, Stephen J. Hill
Summary: The organization of G protein-coupled receptors at the plasma membrane has been a recent focus. Studies on the adenosine A(3) receptor and its mutant R108A reveal differences in membrane organization and downstream signaling, but both receptors can recruit beta-arrestin upon agonist stimulation, showing that effective G protein signaling is not necessary for membrane reorganization and beta-arrestin recruitment.
Review
Biochemistry & Molecular Biology
Dinesh Kankanamge, Mithila Tennakoon, Ajith Karunarathne, N. Gautam
Summary: This review focuses on the current knowledge about the potential roles and mechanisms of the gamma subunits of heterotrimeric G proteins. Loss or dysregulation of specific gamma subunit types can result in different phenotypes and even cancers. Imaging studies have revealed that the membrane affinity of gamma subunits controls the sensitivity and adaptation of cells to external signals.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Genetics & Heredity
Christina M. Campagna, Hayley McMahon, Inna Nechipurenko
Summary: This study reveals the role of RIC-8 protein in cilia membrane morphogenesis in certain nematode sensory neurons. RIC-8 interacts with AGS-3 and ODR-3 to shape cilia morphology through a non-canonical G protein signaling pathway.
Article
Biology
Alastair C. Keen, Maria Hauge Pedersen, Laura Lemel, Daniel J. Scott, Meritxell Canals, Dene R. Littler, Travis Beddoe, Yuki Ono, Lei Shi, Asuka Inoue, Jonathan A. Javitch, J. Robert Lane
Summary: Understanding the signaling of heterotrimeric G proteins is crucial for understanding physiological responses. Pertussis toxin has been widely used to inhibit G alpha(i/o) G proteins, but its effectiveness against G alpha(z) has been limited. A recently discovered toxin, OZITX, has been found to specifically inhibit both G alpha(i/o) and G alpha(z) G proteins, providing a new tool to study their signaling.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Selma E. Anton, Charlotte Kayser, Isabella Maiellaro, Katarina Nemec, Jan Moeller, Andreas Koschinski, Manuela Zaccolo, Paolo Annibale, Martin Falcke, Martin J. Lohse, Andreas Bock
Summary: Cells use independent cAMP nanodomains to send different signals, which form self-sufficient cell signaling units. Each nanodomain contains a highly localized cAMP pool that is protected from other receptors and cell compartments. The gradients of local cAMP concentrations define the size of each individual nanodomain. The coexistence of many such nanodomains allows a single cell to operate multiple independent cellular signals simultaneously.
Article
Pharmacology & Pharmacy
Rafael Franco, Rafael Rivas-Santisteban, Irene Reyes-Resina, Gemma Navarro
Summary: Biased signaling refers to different signaling outputs depending on the chemical structure of the agonist, providing promise for new drug development strategies. This bias can be explained by the induced fit hypothesis and the key/lock hypothesis, and is influenced by the specific agonist.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Shizhong A. Dai, Qi Hu, Rong Gao, Emily E. Blythe, Kouki K. Touhara, Hayden Peacock, Ziyang Zhang, Mark von Zastrow, Hiroaki Suga, Kevan M. Shokat
Summary: This article explores a chemical library of 1012 cyclic peptides and identifies two macrocyclic peptides, GN13 and GD20, that can antagonize the activity and inactive states of the key protein Gas in the G protein-coupled receptor cascade. These macrocyclic peptides have high selectivity and specificity and can modulate cellular signaling through binding to crystallographically defined pockets.
Article
Cell Biology
Anubha Seth, Marius Landau, Andrej Shevchenko, Sofia Traikov, Anita Schultz, Sherif Elsabbagh, Joachim E. Schultz
Summary: This study discovered a new dimension of intracellular AC regulation by chemically defined glycerophospholipids. It was found that a specific glycerophospholipid could significantly enhance the activity of several AC isoforms, and this effect was reversible. However, this glycerophospholipid did not affect extracellular cAMP generation, suggesting an intracellular role.
CELLULAR SIGNALLING
(2022)
Review
Pharmacology & Pharmacy
David J. Marcus, Michael R. Bruchas
Summary: Despite the fact that G protein-coupled receptors (GPCRs) are targeted by about 40% of FDA-approved drugs, there is still a lack of understanding of their physiological and functional roles at the systems level. Classic pharmacological experiments and in vitro assays have provided insights into GPCR signaling cascades, but the interaction of these cascades across different cell types, tissues, and organ systems remains unclear. The development of optical tools has allowed researchers to investigate GPCR signaling in vivo and in vitro, providing temporal and spatial resolution. These tools have been used to explore the functional roles of different populations of GPCRs and their signaling cascades at the systems level.
PHARMACOLOGICAL REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Eri Kitayama, Maki Kimura, Takehito Ouchi, Masahiro Furusawa, Yoshiyuki Shibukawa
Summary: This study investigated the dynamics of intracellular cAMP in cultured human odontoblasts to understand the detailed expression patterns and role of the intracellular cAMP signaling pathway. The results showed the presence of G(alpha)s protein and various receptors (IP, 5-HT4, D-1, A(2A), and VIP) in odontoblasts. Activation of these receptors increased intracellular cAMP levels by activating AC, and this increase was inhibited by an AC inhibitor and receptor antagonists.
Article
Chemistry, Medicinal
Esteban G. Vega Hissi, Antonella B. De Costa Guardamagna, Adriana D. Garro, Cristian R. Falcon, Marko Anderluh, Tihomir Tomasic, Danijel Kikelj, Agustin Yaneff, Carlos A. Davio, Ricardo D. Enriz, Adolfo R. Zurita
Summary: This study reported a derivative of N-(piperidin-4-yl)-1H-pyrrole-2-carboxamide as a new inhibitor for the adenylate cyclase of Giardia lamblia, and developed a model for this specific enzyme. The new inhibitor was found to have a competitive mechanism of action against the enzyme, serving as an excellent starting point for the development of new metabolic inhibitors for G. lamblia.
Article
Cell Biology
Vendula Markova, Lucie Hejnova, Ales Benda, Jiri Novotny, Barbora Melkes
Summary: Beta-arrestins play a crucial role in GPCR-mediated transmembrane signaling processes, but the roles of beta-arrestin 1 and beta-arrestin 2 in MOR-regulated signaling differ, with beta-arrestin 1 more effectively modulating AC activity. This study demonstrates the distinct roles of beta-arrestin isoforms in MOR signaling and reveals their potential interactions with AC.
CELLULAR SIGNALLING
(2021)
Article
Biotechnology & Applied Microbiology
Ting Zhang, Ningchen Zheng, Zhirong Wang, Xuemei Xu
Summary: The multimeric form of SARS-CoV-2 S protein receptor-binding domain (RBD) shows better immunogenicity and induces higher levels of neutralizing antibody responses. A recombinant protein, 2RBDpLC, was constructed by fusing RBD single-chain dimer with a trimerization motif and introducing a cysteine at the C-terminus. It forms RBD dodecamers through trimerization motif and intermolecular disulfide bonds, and exhibits promising potential as a vaccine candidate with the ability to generate cross-neutralizing antibodies against Delta and Omicron variants.
HUMAN VACCINES & IMMUNOTHERAPEUTICS
(2023)