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Title: The structure and function of the vasopressin V₁a receptor
Author: Logan, Richard Thomas
ISNI:       0000 0004 2730 5461
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2013
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The neurohypophysial hormone [arginine⁸]vasopressin (AVP) exerts the majority of its physiological roles through the G-protein-coupled receptor, V₁a R. AVP binding to the V₁a R promotes receptor activation and generates signalling though the inositol phosphate pathway. ICL 2 has been implicated in many aspects of GPCR signalling and crystallographic data highlight the structurally dynamic nature of this region. A complete alanine-scanning study of ICL 2 has not previously been conducted in a GPCR but is presented here in the prototypical peptide-ligand GPCR, V₁a R. However, a role of Leu³.⁵⁸ in mediating G-protein-dependent signalling was observed in the V₁a R – a finding that has previously been reported in other GPCRs. Upon agonist binding, the structural rearrangements of TM V and TM VI are integral in signal transduction in GPCRs. Two highly conserved residues, Tyr⁵.⁵⁸ and Ile⁶.⁴⁰ are key players in the activation process. Given their high conservation, it was presumed that their roles are universal throughout the rhodopsin-like GPCR family. The systematic substitution of these two residues in the V₁a R demonstrate the receptor-specific nature of substitutions of Tyr⁵.⁵⁸ and Ile⁶.⁴⁰ given that findings in the V₁a R are not recapitulated in the generally limited mutagenic studies in other receptors.
Supervisor: Not available Sponsor: Biotechnology and Biological Sciences Research Council (BBSRC) ; Schering-Plough
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QH301 Biology