Conopressin-T from Conus tulipa reveals an antagonist switch in vasopressin-like peptides

Dutertre, Sebastien, Croker, Daniel, Daly, Norelle L., Andersson, Asa, Muttenthaler, Markus, Lumsden, Natalie G., Craik, David J., Alewood, Paul F., Guillon, Gilles, and Lewis, Richard J. (2008) Conopressin-T from Conus tulipa reveals an antagonist switch in vasopressin-like peptides. Journal of Biological Chemistry, 283 (11). pp. 7100-7108.

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Abstract

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 V 1a 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 V 1a receptors, an L7P analogue had increased affinity for the V 1a 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 V 1a 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 V 1a receptor.

Item ID: 27104
Item Type: Article (Research - C1)
ISSN: 1083-351X
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Date Deposited: 11 Jun 2013 06:02
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110106 Medical Biochemistry: Proteins and Peptides (incl Medical Proteomics) @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 100%
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