ArticleProtein science : a publication of the Protein Society2013
Selective CGRP and adrenomedullin peptide binding by tethered RAMP-calcitonin receptor-like receptor extracellular domain fusion proteins.
Article in Protein science : a publication of the Protein Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Nano-to-macroscale dual core-shell structured bioartificial ligament improves outcomes of anterior cruciate ligament reconstruction in rats: A proof-of-concept study.Bioactive materials · 2026Article
- Characterization of the Two-Domain Peptide Binding Mechanism of the Human CGRP Receptor for CGRP and the Ultrahigh Affinity ssCGRP Variant.Biochemistry · 2025Article
- The cell adhesion molecule CD44 acts as a modulator of 5-HT7 receptor functions.Cell communication and signaling : CCS · 2024Article
- CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond.Physiological reviews · 2023Review
- Adrenomedullin 2/intermedin is a slow off-rate, long-acting endogenous agonist of the adrenomedullinbioRxiv : the preprint server for biology · 2023Article
- Modulating effects of RAMPs on signaling profiles of the glucagon receptor family.Acta pharmaceutica Sinica. B · 2022Article
- The Effects of Calcitonin Gene-Related Peptide on Bone Homeostasis and Regeneration.Current osteoporosis reports · 2020Review
- Picomolar Affinity Antagonist and Sustained Signaling Agonist Peptide Ligands for the Adrenomedullin and Calcitonin Gene-Related Peptide Receptors.ACS pharmacology & translational science · 2020Article
- Biochemical characterization of G protein coupling to calcitonin gene-related peptide and adrenomedullin receptors using a native PAGE assay.The Journal of biological chemistry · 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
- Organoid culture media formulated with growth factors of defined cellular activity.Scientific reports · 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
- 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
- N-Glycosylation of Asparagine 130 in the Extracellular Domain of the Human Calcitonin Receptor Significantly Increases Peptide Hormone Affinity.Biochemistry · 2017Article
- Targeting orphan G protein-coupled receptors for the treatment of diabetes and its complications: C-peptide and GPR146.Journal of internal medicine · 2017Review
- Impaired Vasodilatory Responses of Omental Arteries to CGRP Family Peptides in Pregnancies Complicated by Fetal Growth Restriction.The Journal of clinical endocrinology and metabolism · 2016Article
- Amylin structure-function relationships and receptor pharmacology: implications for amylin mimetic drug development.British journal of pharmacology · 2016Review
- Calcitonin and Amylin Receptor Peptide Interaction Mechanisms: INSIGHTS INTO PEPTIDE-BINDING MODES AND ALLOSTERIC MODULATION OF THE CALCITONIN RECEPTOR BY RECEPTOR ACTIVITY-MODIFYING PROTEINS.The Journal of biological chemistry · 2016Article
- Receptor Activity-Modifying Proteins (RAMPs): New Insights and Roles.Annual review of pharmacology and toxicology · 2016Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) are related peptides that are potent vasodilators. The CGRP and AM receptors are heteromeric protein complexes comprised of a shared calcitonin receptor-like receptor (CLR) subunit and a variable receptor activity modifying protein (RAMP) subunit. RAMP1 enables CGRP binding whereas RAMP2 confers AM specificity. How RAMPs determine peptide selectivity is unclear and the receptor stoichiometries are a topic of debate with evidence for 1:1, 2:2, and 2:1 CLR:RAMP stoichiometries. Here, we describe bacterial production of recombinant tethered RAMP-CLR extracellular domain (ECD) fusion proteins and biochemical characterization of their peptide binding properties. Tethering the two ECDs ensures complex stability and enforces defined stoichiometry. The RAMP1-CLR ECD fusion purified as a monomer, whereas the RAMP2-CLR ECD fusion purified as a dimer. Both proteins selectively bound their respective peptides with affinities in the low micromolar range. Truncated CGRP(27-37) and AM(37-52) fragments were identified as the minimal ECD complex binding regions. The CGRP C-terminal amide group contributed to, but was not required for, ECD binding, whereas the AM C-terminal amide group was essential for ECD binding. Alanine-scan experiments identified CGRP residues T30, V32, and F37 and AM residues P43, K46, I47, and Y52 as critical for ECD binding. Our results identify CGRP and AM determinants for receptor ECD complex binding and suggest that the CGRP receptor functions as a 1:1 heterodimer. In contrast, the AM receptor may function as a 2:2 dimer of heterodimers, although our results cannot rule out 2:1 or 1:1 stoichiometries.
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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.