The family of proglucagon peptides Includes glucagon and glucagon-like peptide 1 (GLP-1), two unique peptides derived from the same prohormone. Despite numerous similarities between the peptides, these have long been viewed as having opposing actions on metabolism. GLP-1 is described as a postprandial hormone that stimulates anabolic actions via insulin, while glucagon is viewed as a fasting hormone that drives catabolic actions to maintain euglycemia. Here, we revisit a classic article in Diabetes that first established that glucagon and GLP-1 have more in common than previously appreciated, including actions at the same receptor. Furthermore, we discuss how the impact of this observation has guided research decades later that has reshaped the view of how proglucagon hormones regulate metabolism.
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http://dx.doi.org/10.2337/dbi23-0014 | DOI Listing |
J Struct Biol
December 2024
Advanced Research Initiative, Institute of Integrated Research, Institute of Science Tokyo, 1-5-45 Yushima Bunkyo-ku 113-8510, Tokyo, Japan. Electronic address:
Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are bioactive lysophospholipids derived from cell membranes that activate the endothelial differentiation gene family of G protein-coupled receptors. Activation of these receptors triggers multiple downstream signaling cascades through G proteins such as Gi/o, Gq/11, and G12/13. Therefore, LPA and S1P mediate several physiological processes, including cytoskeletal dynamics, neurite retraction, cell migration, cell proliferation, and intracellular ion fluxes.
View Article and Find Full Text PDFNat Commun
November 2024
Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
Bitter taste receptors (TAS2Rs), a subfamily of G-protein coupled receptors (GPCRs) expressed orally and extraorally, elicit signaling in response to a large set of tastants. Among 25 functional TAS2Rs encoded in the human genome, TAS2R14 is the most promiscuous, and responds to hundreds of chemically diverse ligands. Here we present the cryo-electron microscopy (cryo-EM) structure of the human TAS2R14 in complex with its signaling partner gustducin, and bound to flufenamic acid (FFA), a clinically approved nonsteroidal anti-inflammatory drug.
View Article and Find Full Text PDFMethods Mol Biol
July 2024
Education and Research Support Center, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
G-protein-coupled receptors (GPCRs) are hepta-helical transmembrane proteins that mediate various intracellular signaling events in response to their specific ligands including many lipid mediators. Although analyses of GPCR molecular interactions are pivotal to understanding diverse intracellular signaling events, affinity purification of interacting proteins by a conventional co-immunoprecipitation method is challenging due to the hydrophobic nature of GPCRs and their dynamic molecular interactions. Proximity labeling catalyzed by a TurboID system is a powerful technique for defining the molecular interactions of target proteins in living cells.
View Article and Find Full Text PDFJ Biol Chem
June 2024
Department of Computational and Quantitative Medicine, Beckman Research Institute of the City of Hope, Duarte, California, USA; Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope, Duarte, California, USA. Electronic address:
Cooperative interactions in protein-protein interfaces demonstrate the interdependency or the linked network-like behavior and their effect on the coupling of proteins. Cooperative interactions also could cause ripple or allosteric effects at a distance in protein-protein interfaces. Although they are critically important in protein-protein interfaces, it is challenging to determine which amino acid pair interactions are cooperative.
View Article and Find Full Text PDFMol Pharmacol
May 2024
Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts (J.S.S., A.S.H., M.A.S., A.N.D., V.G.C.-M., A.C.K.) and Brigham and Women's Hospital, Boston, Massachusetts (J.S.S.)
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