ArticleBiochimica et biophysica acta2011
Extracellular loops 1 and 3 and their associated transmembrane regions of the calcitonin receptor-like receptor are needed for CGRP receptor function.
Article in Biochimica et biophysica acta, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- Cryo-EM Structure of the Human Amylin 1 Receptor in Complex with CGRP and Gs Protein.Biochemistry · 2024Article
- The Role of ICL1 and H8 in Class B1 GPCRs; Implications for Receptor Activation.Frontiers in endocrinology · 2021Article
- Exploring Ligand Binding to Calcitonin Gene-Related Peptide Receptors.Frontiers in molecular biosciences · 2021Article
- Molecular Mechanisms of Class B GPCR Activation: Insights from Adrenomedullin Receptors.ACS pharmacology & translational science · 2020Article
- hThe Journal of experimental medicine · 2018Article
- Cryo-EM structure of the active, GNature · 2018Article
- Extracellular loops 2 and 3 of the calcitonin receptor selectively modify agonist binding and efficacy.Biochemical pharmacology · 2018Article
- Receptor activity-modifying protein dependent and independent activation mechanisms in the coupling of calcitonin gene-related peptide and adrenomedullin receptors to Gs.Biochemical pharmacology · 2017Article
- Article
- Decoding Corticotropin-Releasing Factor Receptor Type 1 Crystal Structures.Current molecular pharmacology · 2017Article
- The Extracellular Surface of the GLP-1 Receptor Is a Molecular Trigger for Biased Agonism.Cell · 2016Article
- Receptor Activity-modifying Proteins 2 and 3 Generate Adrenomedullin Receptor Subtypes with Distinct Molecular Properties.The Journal of biological chemistry · 2016Article
- Receptor Activity-Modifying Proteins (RAMPs): New Insights and Roles.Annual review of pharmacology and toxicology · 2016Review
- An intrinsic agonist mechanism for activation of glucagon-like peptide-1 receptor by its extracellular domain.Cell discovery · 2016Article
- Transmembrane signal transduction by peptide hormones via family B G protein-coupled receptors.Frontiers in pharmacology · 2015Review
- Structural and functional insights into the juxtamembranous amino-terminal tail and extracellular loop regions of class B GPCRs.British journal of pharmacology · 2014Review
- Structure-activity relationships of the N-terminus of calcitonin gene-related peptide: key roles of alanine-5 and threonine-6 in receptor activation.British journal of pharmacology · 2014Article
- The role of ECL2 in CGRP receptor activation: a combined modelling and experimental approach.Journal of the Royal Society, Interface · 2013Article
- Molecular basis for negative regulation of the glucagon receptor.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- The third extracellular loop of the human calcitonin receptor-like receptor is crucial for the activation of adrenomedullin signalling.British journal of pharmacology · 2012Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The first and third extracellular loops (ECL) of G protein-coupled receptors (GPCRs) have been implicated in ligand binding and receptor function. This study describes the results of an alanine/leucine scan of ECLs 1 and 3 and loop-associated transmembrane (TM) domains of the secretin-like GPCR calcitonin receptor-like receptor which associates with receptor activity modifying protein 1 to form the CGRP receptor. Leu195Ala, Val198Ala and Ala199Leu at the top of TM2 all reduced αCGRP-mediated cAMP production and internalization; Leu195Ala and Ala199Leu also reduced αCGRP binding. These residues form a hydrophobic cluster within an area defined as the "minor groove" of rhodopsin-like GPCRs. Within ECL1, Ala203Leu and Ala206Leu influenced the ability of αCGRP to stimulate adenylate cyclase. In TM3, His219Ala, Leu220Ala and Leu222Ala have influences on αCGRP binding and cAMP production; they are likely to indirectly influence the binding site for αCGRP as well as having an involvement in signal transduction. On the exofacial surfaces of TMs 6 and 7, a number of residues were identified that reduced cell surface receptor expression, most noticeably Leu351Ala and Glu357Ala in TM6. The residues may contribute to the RAMP1 binding interface. Ile360Ala impaired αCGRP-mediated cAMP production. Ile360 is predicted to be located close to ECL2 and may facilitate receptor activation. Identification of several crucial functional loci gives further insight into the activation mechanism of this complex receptor system and may aid rational drug design.
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