ArticleProteins2014
Terminal sialic acids on CD44 N-glycans can block hyaluronan binding by forming competing intramolecular contacts with arginine sidechains.
Article in Proteins, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Mammalian Neuraminidases in Immune-Mediated Diseases: Mucins and Beyond.Frontiers in immunology · 2022Pooled it
- Encoding Cell-Surface Receptor Function Through Glycosylation: Lessons From CD44.Chembiochem : a European journal of chemical biology · 2026Review
- LARGE1 processively polymerizes length-controlled matriglycan on prodystroglycan.Nature communications · 2025Article
- The Exploitation of the Glycosylation Pattern in Asthma: How We Alter Ancestral Pathways to Develop New Treatments.Biomolecules · 2024Review
- The role of N-glycosylation modification in the pathogenesis of liver cancer.Cell death & disease · 2023Review
- Hypoxia Controls the Glycome Signature and Galectin-8-Ligand Axis to Promote Protumorigenic Properties of Metastatic Melanoma.The Journal of investigative dermatology · 2023Article
- Sialidase Inhibitors with Different Mechanisms.Journal of medicinal chemistry · 2022Review
- Atomic-Resolution Experimental Structural Biology and Molecular Dynamics Simulations of Hyaluronan and Its Complexes.Molecules (Basel, Switzerland) · 2022Review
- The Association Between Follicular Fluid Sialic Acid Levels, Oocyte Quality, and Pregnancy Rates.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
- O-linked α2,3 sialylation defines stem cell populations in breast cancer.Science advances · 2022Article
- CD44 Glycosylation as a Therapeutic Target in Oncology.Frontiers in oncology · 2022Review
- Molecular Dynamics Simulation Study on Allosteric Regulation of CD44-Hyaluronan Binding as a Force Sensing Mechanism.ACS omega · 2021Article
- N-Glycosylation can selectively block or foster different receptor-ligand binding modes.Scientific reports · 2021Article
- Therapeutic Effect of Neuraminidase-1-Selective Inhibition in Mouse Models of Bleomycin-Induced Pulmonary Inflammation and Fibrosis.The Journal of pharmacology and experimental therapeutics · 2021Article
- The Gardos effect drives erythrocyte senescence and leads to Lu/BCAM and CD44 adhesion molecule activation.Blood advances · 2020Article
- Insight in Adhesion Protein Sialylation and Microgravity Dependent Cell Adhesion-An Omics Network Approach.International journal of molecular sciences · 2020Article
- Atomistic fingerprint of hyaluronan-CD44 binding.PLoS computational biology · 2017Article
- Elevated expression of NEU1 sialidase in idiopathic pulmonary fibrosis provokes pulmonary collagen deposition, lymphocytosis, and fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- A Multichannel Biosensor for Rapid Determination of Cell Surface Glycomic Signatures.ACS central science · 2015Article
- Investigation of Carbohydrate Recognition via Computer Simulation.Molecules (Basel, Switzerland) · 2015Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Specific sugar residues and their linkages form the basis of molecular recognition for interactions of glycoproteins with other biomolecules. Seemingly small changes, like the addition of a single monosaccharide in the covalently attached glycan component of glycoproteins, can greatly affect these interactions. For instance, the sialic acid capping of glycans affects protein-ligand binding involved in cell-cell and cell-matrix interactions. CD44 is a single-pass transmembrane glycoprotein whose binding with its carbohydrate ligand hyaluronan (HA), an extracellular matrix component, mediates processes such as leukocyte homing, cell adhesion, and tumor metastasis. This binding is highly regulated by glycosylation of the N-terminal extracellular hyaluronan-binding domain (HABD); specifically, sialic acid capped N-glycans of HABD inhibit ligand binding. However, the molecular mechanism behind this sialic acid mediated regulation has remained unknown. Two of the five N-glycosyation sites of HABD have been previously identified as having the greatest inhibitory effect on HA binding, but only if the glycans contain terminal sialic acid residues. These two sites, Asn25 and Asn120, were chosen for in silico glycosylation in this study. Here, from extensive standard molecular dynamics simulations and biased simulations, we propose a molecular mechanism for this behavior based on spontaneously-formed charge-paired hydrogen bonding interactions between the negatively-charged sialic acid residues and positively-charged Arg sidechains known to be critically important for binding to HA, which itself is negatively charged. Such intramolecular hydrogen bonds would preclude associations critical to hyaluronan binding. This observation suggests how CD44 and related glycoprotein binding is regulated by sialylation as cellular environments fluctuate.
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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.