Cited by 270Receptor Mechanisms and SignalingNeuroendocrine regulation and behaviorNeuropeptides and Animal Physiology

The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.

The Binding Site of Neuropeptide Vasopressin V1a Receptor

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Abstract

To identify receptor functional domains underlying binding of the neurohypophysial hormones vasopressin (AVP) and oxytocin (OT), we have constructed a three-dimensional (3D) model of the V1a vasopressin receptor subtype and docked the endogenous ligand AVP. To verify and to refine the 3D model, residues likely to be involved in agonist binding were selected for site-directed mutagenesis. Our experimental results suggest that AVP, which is characterized by a cyclic structure, could be completely buried into a 15-20-A deep cleft defined by the transmembrane helices of the receptor and interact with amino acids located within this region. Moreover, the AVP-binding site is situated in a position equivalent to that described for the cationic neurotransmitters. Since all mutated residues are highly conserved in AVP and OT receptors, we propose that the same agonist-binding site is shared by all members of this receptor family. In contrast, the affinity for the antagonists tested, including those with a structure closely related to AVP, is not affected by mutations. This indicates a different binding mode for agonists and antagonists in the vasopressin receptor.

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  1. Hibert, 1991, Mol. Pharmacol., 40, 8
  2. Fraser, 1989, Mol. Pharmacol., 36, 840

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Items 201–270 of 270

Metadata

Authors
Mouillac, B., Chini, B., Balestre, M.-N., Elands, J., Trumpp-Kallmeyer, S., Hoflack, J., Hibert, M., Jard, S., & Barberis, C.
Affiliations
Centre National de la Recherche Scientifique (FR)
Corresponding author
Barberis, Claude
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1995-10
Volume
270
Issue
43
Pages
25771-25777
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2062176518
Cited by
262
References
41
Citations by year
2026: 2 · 2025: 5 · 2024: 1 · 2023: 1 · 2022: 6 · 2021: 5 · 2020: 8 · 2019: 6 · 2018: 2 · 2017: 5 · 2016: 4 · 2015: 2 · 2014: 4 · 2013: 8 · 2012: 8
FWCI
5.71
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Institut National de la Santé et de la Recherche Médicale
  • Centre National de la Recherche Scientifique
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
vasopressin V1a receptor, vasopressin, oxytocin, receptor binding sites, agonist binding, antagonist binding, protein-ligand docking, site-directed mutagenesis, transmembrane helices, cyclic peptide ligands, neurohypophyseal hormones
MeSH terms
Amino Acid Sequence, Animals, Arginine Vasopressin, Binding Sites, Computer Simulation, DNA Mutational Analysis, Models, Molecular, Molecular Sequence Data, Type C Phospholipases, Protein Binding, Protein Conformation, Radioligand Assay, Recombinant Proteins, Structure-Activity Relationship, Signal Transduction, Mutagenesis, Site-Directed, Sequence Homology, Amino Acid, Receptors, Vasopressin, Receptors, Oxytocin, Rats

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