ArticleBiochemistry2025
Characterization of the Two-Domain Peptide Binding Mechanism of the Human CGRP Receptor for CGRP and the Ultrahigh Affinity ssCGRP Variant.
Article in Biochemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed.
- Immune remodeling and metabolic reprogramming in chronic fatigue: insights into GPCR signaling and epigenetic regulation.Frontiers in immunology · 2026Review
- Copper only SOD repeat proteins likely act as an extracellular superoxide dismutase in oyster antioxidant defense.Scientific reports · 2025Article
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Authors and funding
5 authors.
Funding
Abstract
Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide that functions in pain signaling and neuroimmune communication. The CGRP receptor, CGRPR, is a class B GPCR that is a drug target for migraine headache and other disorders. Here, we used nanoBRET receptor binding and cAMP biosensor signaling assays and theoretical modeling to characterize the CGRPR "two-domain" peptide binding mechanism. Single-site extracellular domain (ECD)-binding and two-site ECD/transmembrane domain (TMD)-binding peptides were examined for CGRP and a high-affinity variant "ssCGRP" with modifications in the C-terminal region. Wildtype and ssCGRP(27-37) bound the ECD with affinities of 1 μM and 0.5 nM, and residence times of 5 s and 8 min, respectively. The (8-37) antagonist fragments had affinities of 100 nM for wildtype and 0.5 nM for ss and exhibited behavior consistent with two-site ECD/TMD binding. ssCGRP(8-37) had a residence time of 76 min. CGRP(1-37) agonist had 25-fold higher affinity for the G protein-coupled state of the CGRPR (
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