ArticleJournal of the Royal Society, Interface2013
Similarity between class A and class B G-protein-coupled receptors exemplified through calcitonin gene-related peptide receptor modelling and mutagenesis studies.
Article in Journal of the Royal Society, Interface, 2013. 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, 48 citations in OpenAlex.
- CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond.Physiological reviews · 2023Review
- Protons taken hostage: Dynamic H-bond networks of the pH-sensing GPR68.Computational and structural biotechnology journal · 2023Article
- Dynamics of GLP-1R peptide agonist engagement are correlated with kinetics of G protein activation.Nature communications · 2022Article
- The Role of ICL1 and H8 in Class B1 GPCRs; Implications for Receptor Activation.Frontiers in endocrinology · 2021Article
- Structure and Dynamics of Adrenomedullin Receptors AMACS pharmacology & translational science · 2020Article
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- Cryo-EM structure of the active, GNature · 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
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- Genetically encoded photocross-linkers determine the biological binding site of exendin-4 peptide in the N-terminal domain of the intact human glucagon-like peptide-1 receptor (GLP-1R).The Journal of biological chemistry · 2017Article
- Key interactions by conserved polar amino acids located at the transmembrane helical boundaries in Class B GPCRs modulate activation, effector specificity and biased signalling in the glucagon-like peptide-1 receptor.Biochemical pharmacology · 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
- Transmembrane signal transduction by peptide hormones via family B G protein-coupled receptors.Frontiers in pharmacology · 2015Review
- Structure of Class B GPCRs: new horizons for drug discovery.British journal of pharmacology · 2014Review
- Structural and functional insights into the juxtamembranous amino-terminal tail and extracellular loop regions of class B GPCRs.British journal of pharmacology · 2014Review
- Do plants contain g protein-coupled receptors?Plant physiology · 2014Article
- The role of ECL2 in CGRP receptor activation: a combined modelling and experimental approach.Journal of the Royal Society, Interface · 2013Article
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Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Modelling class B G-protein-coupled receptors (GPCRs) using class A GPCR structural templates is difficult due to lack of homology. The plant GPCR, GCR1, has homology to both class A and class B GPCRs. We have used this to generate a class A-class B alignment, and by incorporating maximum lagged correlation of entropy and hydrophobicity into a consensus score, we have been able to align receptor transmembrane regions. We have applied this analysis to generate active and inactive homology models of the class B calcitonin gene-related peptide (CGRP) receptor, and have supported it with site-directed mutagenesis data using 122 CGRP receptor residues and 144 published mutagenesis results on other class B GPCRs. The variation of sequence variability with structure, the analysis of polarity violations, the alignment of group-conserved residues and the mutagenesis results at 27 key positions were particularly informative in distinguishing between the proposed and plausible alternative alignments. Furthermore, we have been able to associate the key molecular features of the class B GPCR signalling machinery with their class A counterparts for the first time. These include the [K/R]KLH motif in intracellular loop 1, [I/L]xxxL and KxxK at the intracellular end of TM5 and TM6, the NPXXY/VAVLY motif on TM7 and small group-conserved residues in TM1, TM2, TM3 and TM7. The equivalent of the class A DRY motif is proposed to involve Arg(2.39), His(2.43) and Glu(3.46), which makes a polar lock with T(6.37). These alignments and models provide useful tools for understanding class B GPCR function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.