Conopressin-T from Conus tulipa Reveals an Antagonist Switch in Vasopressin-like Peptides
| Autor: | Gilles Guillon, Åsa Andersson, Richard J. Lewis, Sébastien Dutertre, Natalie G. Lumsden, Markus Muttenthaler, Daniel E. Croker, Norelle L. Daly, Paul F. Alewood, David J. Craik |
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| Přispěvatelé: | Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Institute for Molecular Bioscience, University of Queensland [Brisbane], Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dutertre, Sébastien |
| Rok vydání: | 2008 |
| Předmět: |
Agonist
Receptors Vasopressin Vasopressin Vasopressins Stereochemistry medicine.drug_class Inositol Phosphates [CHIM.THER] Chemical Sciences/Medicinal Chemistry Vasotocin CHO Cells [CHIM.THER]Chemical Sciences/Medicinal Chemistry Tripeptide Oxytocin Models Biological Biochemistry 03 medical and health sciences chemistry.chemical_compound Cricetulus 0302 clinical medicine Cricetinae Arginine vasopressin receptor 2 medicine Animals Humans Receptor Molecular Biology 030304 developmental biology 0303 health sciences biology Conus tulipa Conus Snail Cell Biology biology.organism_classification [SDV.TOX] Life Sciences [q-bio]/Toxicology chemistry Receptors Oxytocin [SDV.TOX]Life Sciences [q-bio]/Toxicology Vasopressin Analogue Peptides 030217 neurology & neurosurgery |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2008, 283 (11), pp.7100-7108. ⟨10.1074/jbc.M706477200⟩ Journal of Biological Chemistry, 2008, 283 (11), pp.7100-7108. ⟨10.1074/jbc.M706477200⟩ |
| ISSN: | 0021-9258 1083-351X |
| DOI: | 10.1074/jbc.m706477200 |
| Popis: | International audience; We report the discovery of conopressin-T, a novel bioactive peptide isolated from Conus tulipa venom. Conopressin-T belongs to the vasopressin-like peptide family and displays high sequence homology to the mammalian hormone oxytocin (OT) and to vasotocin, the endogenous vasopressin analogue found in teleost fish, the cone snail's prey. Conopressin-T was found to act as a selective antagonist at the human V1a receptor. All peptides in this family contain two conserved amino acids within the exocyclic tripeptide (Pro7 and Gly9), which are replaced with Leu7 and Val9 in conopressin-T. Whereas conopressin-T binds only to OT and V1a receptors, an L7P analogue had increased affinity for the V1a receptor and weak V2 receptor binding. Surprisingly, replacing Gly9 with Val9 in OT and vasopressin revealed that this position can function as an agonist/antagonist switch at the V1a receptor. NMR structures of both conopressin-T and L7P analogue revealed a marked difference in the orientation of the exocyclic tripeptide that may serve as templates for the design of novel ligands with enhanced affinity for the V1a receptor. |
| Databáze: | OpenAIRE |
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