ArticleJournal of molecular biology2020
Calcitonin Receptor N-Glycosylation Enhances Peptide Hormone Affinity by Controlling Receptor Dynamics.
Article in Journal of molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 50 citations in OpenAlex.
- PACAP versus CGRP in migraine: From mouse models to clinical translation.Cephalalgia : an international journal of headache · 2025Review
- Amylin Receptor 1 Mutagenesis Revealed a Potential Role of Calcitonin Serine 29 in Receptor Interaction.Biomedicines · 2025Article
- Deglycosylation and truncation in the neuraminidase stalk are functionally equivalent in enhancing the pathogenicity of a high pathogenicity avian influenza virus in chickens.Journal of virology · 2025Article
- Structural and Functional Glycosylation of the Abdala COVID-19 Vaccine.Glycobiology · 2025Article
- Research progress of diabetic osteoporosis: a comprehensive review.Frontiers in endocrinology · 2025Review
- Conformational dynamics underlying atypical chemokine receptor 3 activation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Intricacies of Renal Phosphate Reabsorption-An Overview.International journal of molecular sciences · 2024Review
- Osteoporosis treatment: current drugs and future developments.Frontiers in pharmacology · 2024Review
- Glycosylation and Crowded Membrane Effects on Influenza Neuraminidase Stability and Dynamics.The journal of physical chemistry letters · 2023Article
- Calcitonin/PACTrends in pharmacological sciences · 2023Review
- New Insights into the Structure and Function of Class B1 GPCRs.Endocrine reviews · 2023Article
- Enrichment and fragmentation approaches for enhanced detection and characterization of endogenous glycosylated neuropeptides.Proteomics · 2023Article
- Deficiency of N-linked glycosylation impairs immune function of B7-H6.Frontiers in immunology · 2023Article
- Towards Precision Oncology: The Role of Smoothened and Its Variants in Cancer.Journal of personalized medicine · 2022Review
- Hyaluronic acid-GPRC5C signalling promotes dormancy in haematopoietic stem cells.Nature cell biology · 2022Article
- Advances in Hydrogen/Deuterium Exchange Mass Spectrometry and the Pursuit of Challenging Biological Systems.Chemical reviews · 2022Review
- Mediators of Amylin Action in Metabolic Control.Journal of clinical medicine · 2022Review
- Development of High Affinity Calcitonin Analog Fragments Targeting Extracellular Domains of Calcitonin Family Receptors.Biomolecules · 2021Article
- A genome-wide scan to identify signatures of selection in two Iranian indigenous chicken ecotypes.Genetics, selection, evolution : GSE · 2021Article
- Association of hyperglycaemia with hospital mortality in nondiabetic COVID-19 patients: A cohort study.Diabetes & metabolism · 2021Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR) is a drug target for osteoporosis and diabetes. N-glycosylation of asparagine 130 in its extracellular domain (ECD) enhances calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism. Here, we present two crystal structures of salmon calcitonin-bound, GlcNAc-bearing CTR ECD at 1.78 and 2.85 Å resolutions and analyze the mechanism of the glycan effect. The N130 GlcNAc does not contact the hormone. Surprisingly, the structures are nearly identical to a structure of hormone-bound, N-glycan-free ECD, which suggested that the GlcNAc might affect CTR dynamics not observed in the static crystallographic snapshots. Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site while increasing flexibility of the peptide-binding site turret loop. These changes due to N-glycosylation increased the ligand on-rate and decreased its off-rate. The glycan effect extended to RAMP-CTR amylin receptor complexes and was also conserved in the related CGRP receptor. These results reveal that N-glycosylation can modulate GPCR function by altering receptor dynamics.
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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.