ArticleThe Journal of biological chemistry2016
Receptor Activity-modifying Proteins 2 and 3 Generate Adrenomedullin Receptor Subtypes with Distinct Molecular Properties.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- The circularly permuted globin domain of androglobin exhibits atypical heme stabilization and nitric oxide interaction.Chemical science · 2024Article
- Cryo-EM Structure of the Human Amylin 1 Receptor in Complex with CGRP and Gs Protein.Biochemistry · 2024Article
- Pharmacological characterisation of mouse calcitonin and calcitonin receptor-like receptors reveals differences compared with human receptors.British journal of pharmacology · 2022Article
- Modulating effects of RAMPs on signaling profiles of the glucagon receptor family.Acta pharmaceutica Sinica. B · 2022Article
- "ADPKD-omics": determinants of cyclic AMP levels in renal epithelial cells.Kidney international · 2022Review
- Adrenomedullin protects rat dorsal root ganglion neurons against doxorubicin-induced toxicity by ameliorating oxidative stress.Iranian journal of basic medical sciences · 2020Article
- Identification of Small-Molecule Positive Modulators of Calcitonin-like Receptor-Based Receptors.ACS pharmacology & translational science · 2020Article
- Structure and Dynamics of Adrenomedullin Receptors AMACS pharmacology & translational science · 2020Article
- Molecular Mechanisms of Class B GPCR Activation: Insights from Adrenomedullin Receptors.ACS pharmacology & translational science · 2020Article
- Targeting Adrenomedullin in Oncology: A Feasible Strategy With Potential as Much More Than an Alternative Anti-Angiogenic Therapy.Frontiers in oncology · 2020Review
- RAMPs as allosteric modulators of the calcitonin and calcitonin-like class B G protein-coupled receptors.Advances in pharmacology (San Diego, Calif.) · 2020Review
- Shear stress-induced endothelial adrenomedullin signaling regulates vascular tone and blood pressure.The Journal of clinical investigation · 2019Article
- Deconvoluting the Molecular Control of Binding and Signaling at the Amylin 3 Receptor: RAMP3 Alters Signal Propagation through Extracellular Loops of the Calcitonin Receptor.ACS pharmacology & translational science · 2019Article
- The Molecular Control of Calcitonin Receptor Signaling.ACS pharmacology & translational science · 2019Article
- Structure-function analyses reveal a triple β-turn receptor-bound conformation of adrenomedullin 2/intermedin and enable peptide antagonist design.The Journal of biological chemistry · 2018Article
- Molecular Signature for Receptor Engagement in the Metabolic Peptide Hormone Amylin.ACS pharmacology & translational science · 2018Article
- 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
- Probing the Mechanism of Receptor Activity-Modifying Protein Modulation of GPCR Ligand Selectivity through Rational Design of Potent Adrenomedullin and Calcitonin Gene-Related Peptide Antagonists.Molecular pharmacology · 2018Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
Abstract
Adrenomedullin (AM) is a peptide hormone with numerous effects in the vascular systems. AM signals through the AM1 and AM2 receptors formed by the obligate heterodimerization of a G protein-coupled receptor, the calcitonin receptor-like receptor (CLR), and receptor activity-modifying proteins 2 and 3 (RAMP2 and RAMP3), respectively. These different CLR-RAMP interactions yield discrete receptor pharmacology and physiological effects. The effective design of therapeutics that target the individual AM receptors is dependent on understanding the molecular details of the effects of RAMPs on CLR. To understand the role of RAMP2 and -3 on the activation and conformation of the CLR subunit of AM receptors, we mutated 68 individual amino acids in the juxtamembrane region of CLR, a key region for activation of AM receptors, and determined the effects on cAMP signaling. Sixteen CLR mutations had differential effects between the AM1 and AM2 receptors. Accompanying this, independent molecular modeling of the full-length AM-bound AM1 and AM2 receptors predicted differences in the binding pocket and differences in the electrostatic potential of the two AM receptors. Druggability analysis indicated unique features that could be used to develop selective small molecule ligands for each receptor. The interaction of RAMP2 or RAMP3 with CLR induces conformational variation in the juxtamembrane region, yielding distinct binding pockets, probably via an allosteric mechanism. These subtype-specific differences have implications for the design of therapeutics aimed at specific AM receptors and for understanding the mechanisms by which accessory proteins affect G protein-coupled receptor function.
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