ArticleScientific reports2021
N-Glycosylation can selectively block or foster different receptor-ligand binding modes.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Encoding Cell-Surface Receptor Function Through Glycosylation: Lessons From CD44.Chembiochem : a European journal of chemical biology · 2026Review
- Glycosylation-modulated conformational diversity in neurotrophin receptors.Biophysical journal · 2026Article
- Cross-talk between glycosylation pathways: Mechanistic insights and implications for human diseases.Molecular metabolism · 2026Review
- A Chemoenzymatic Method To Systematically Quantify Core Fucosylation Stoichiometry of Glycoproteins and Reveal Its Roles in EMT and Embryonic Development.Analytical chemistry · 2026Article
- CD44 as a Central Integrator of Inflammation and Fibrosis: From Molecular Signaling to Environmental Modulation.International journal of molecular sciences · 2025Review
- Rhesus Macaque Killer Cell Ig-like Receptor Domain 0 Glycans Impact Surface Expression and Ligand Specificity.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Refined Protein-Sugar Interactions in the Martini Force Field.Journal of chemical theory and computation · 2024Article
- Deciphering Drug Resistance: Investigating the Emerging Role of Hyaluronan Metabolism and Signaling and Tumor Extracellular Matrix in Cancer Chemotherapy.International journal of molecular sciences · 2024Review
- CD44 in Bladder Cancer.Cancers · 2024Review
- Multiple circulating forms of neprilysin detected with novel epitope-directed monoclonal antibodies.Cellular and molecular life sciences : CMLS · 2024Article
- Metabolism-driven glycosylation represents therapeutic opportunities in interstitial lung diseases.Frontiers in immunology · 2024Review
- Article
- CD44: a cancer stem cell marker and therapeutic target in leukemia treatment.Frontiers in immunology · 2024Review
- Cancer-specific glycosylation of CD13 impacts its detection and activity in preclinical cancer tissues.iScience · 2023Article
- Truncation of GalNAc-type O-glycans Suppresses CD44-mediated Osteoclastogenesis and Bone Metastasis in Breast Cancer.Molecular cancer research : MCR · 2023Article
- The role of N-glycosylation modification in the pathogenesis of liver cancer.Cell death & disease · 2023Review
- Role of CD44 isoforms in epithelial-mesenchymal plasticity and metastasis.Clinical & experimental metastasis · 2022Review
- Comparison of self-sampling blood collection for N-glycosylation analysis.BMC research notes · 2022Article
- SARS-CoV-2 spike binding to ACE2 is stronger and longer ranged due to glycan interaction.Biophysical journal · 2022Article
- Use of Raman and Raman optical activity to extract atomistic details of saccharides in aqueous solution.PLoS computational biology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While DNA encodes protein structure, glycans provide a complementary layer of information to protein function. As a prime example of the significance of glycans, the ability of the cell surface receptor CD44 to bind its ligand, hyaluronan, is modulated by N-glycosylation. However, the details of this modulation remain unclear. Based on atomistic simulations and NMR, we provide evidence that CD44 has multiple distinct binding sites for hyaluronan, and that N-glycosylation modulates their respective roles. We find that non-glycosylated CD44 favors the canonical sub-micromolar binding site, while glycosylated CD44 binds hyaluronan with an entirely different micromolar binding site. Our findings show (for the first time) how glycosylation can alter receptor affinity by shielding specific regions of the host protein, thereby promoting weaker binding modes. The mechanism revealed in this work emphasizes the importance of glycosylation in protein function and poses a challenge for protein structure determination where glycosylation is usually neglected.
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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.