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The role of ECL2 in CGRP receptor activation: a combined modelling and experimental approach

Woolley, Michael J and Watkins, Harriet A and Taddese, Bruck and Karakullukcu, Z Gamze and Barwell, James and Smith, Kevin J and Hay, Debbie L and Poyner, David R and Reynolds, Christopher A and Conner, Alex C (2013) 'The role of ECL2 in CGRP receptor activation: a combined modelling and experimental approach.' Journal of The Royal Society Interface, 10 (88). p. 20130589. ISSN 1742-5689

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<jats:p>The calcitonin gene-related peptide (CGRP) receptor is a complex of a calcitonin receptor-like receptor (CLR), which is a family B G-protein-coupled receptor (GPCR) and receptor activity modifying protein 1. The role of the second extracellular loop (ECL2) of CLR in binding CGRP and coupling to Gs was investigated using a combination of mutagenesis and modelling. An alanine scan of residues 271–294 of CLR showed that the ability of CGRP to produce cAMP was impaired by point mutations at 13 residues; most of these also impaired the response to adrenomedullin (AM). These data were used to select probable ECL2-modelled conformations that are involved in agonist binding, allowing the identification of the likely contacts between the peptide and receptor. The implications of the most likely structures for receptor activation are discussed.</jats:p>

Item Type: Article
Uncontrolled Keywords: calcitonin gene-related peptide; class B G-protein-coupled receptor; loop modelling; site-directed mutagenesis; calcitonin receptor-like receptor
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 18 Oct 2013 10:52
Last Modified: 18 Aug 2022 11:15

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