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

Woolley, MJ and Watkins, HA and Taddese, B and Karakullukcu, ZG and Barwell, J and Smith, KJ and Hay, DL and Poyner, DR and Reynolds, CA and Conner, AC (2013) 'The role of ECL2 in CGRP receptor activation: A combined modelling and experimental approach.' Journal of the Royal Society Interface, 10 (88). ISSN 1742-5689

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Abstract

The calcitonin gene-related peptide (CGRP) receptor is a complex of a cal-citonin 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. © 2013 The Authors.

Item Type: Article
Subjects: Q Science > QH Natural history > QH426 Genetics
Depositing User: Jim Jamieson
Date Deposited: 18 Oct 2013 10:52
Last Modified: 01 Aug 2019 13:18
URI: http://repository.essex.ac.uk/id/eprint/8186

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