ArticleThe Journal of biological chemistry2013
How natalizumab binds and antagonizes α4 integrins.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 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
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Molecular insights into glial neuroimmune cross reactivity with CNS antigens and its role in neuroinflammation.Inflammopharmacology · 2026Pooled it
- Pharmacokinetics and Pharmacodynamics of Natalizumab 6-Week Dosing vs Continued 4-Week Dosing for Relapsing-Remitting Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2024Trial
- Identification of New Regions in HIV-1 gp120 Variable 2 and 3 Loops that Bind to α4β7 Integrin Receptor.PloS one · 2015Trial
- Shared ligand-blocking mechanism but distinct conformational modulation by α5-targeting antibodies BIIG2 and MINT1526A.Structure (London, England : 1993) · 2026Article
- Impact of Anti-CD20 Therapies on Cytokine, Chemokine and Adhesion Molecule Dynamics in Multiple Sclerosis: A Narrative Review.Neurology and therapy · 2026Review
- Clinical implications of natalizumab Fab-arm exchange in patients with multiple sclerosis.Frontiers in immunology · 2026Article
- Therapeutic Effect of a Recombinant Human Fibronectin Construct in Skeletal Muscle Repair and Oxidative Stress.International journal of molecular sciences · 2025Article
- DNA Aptamer-Polymer Conjugates for Selective Targeting of Integrin α4β1ACS applied materials & interfaces · 2025Article
- Human ITGAV variants are associated with immune dysregulation, brain abnormalities, and colitis.The Journal of experimental medicine · 2024Article
- Structural insights into the molecular recognition of integrin αVβ3 by RGD-containing ligands: The role of the specificity-determining loop (SDL).bioRxiv : the preprint server for biology · 2024Article
- T cell trafficking in human chronic inflammatory diseases.iScience · 2024Review
- Androgen deprivation therapy exacerbates Alzheimer's-associated cognitive decline via increased brain immune cell infiltration.Science advances · 2024Article
- Conjecturing about Small-Molecule Agonists and Antagonists of α4β1 Integrin: From Mechanistic Insight to Potential Therapeutic Applications.Biomedicines · 2024Review
- Targeting T-cell integrins in autoimmune and inflammatory diseases.Clinical and experimental immunology · 2024Review
- Understanding the molecular mechanisms of anti-trafficking therapies and their clinical relevance in inflammatory bowel disease.Mucosal immunology · 2023Review
- Integrin signaling in cancer: bidirectional mechanisms and therapeutic opportunities.Cell communication and signaling : CCS · 2023Review
- Targeting integrin pathways: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2023Review
- Microglial crosstalk with astrocytes and immune cells in amyotrophic lateral sclerosis.Frontiers in immunology · 2023Review
- Review
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Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Natalizumab antibody to α4-integrins is used in therapy of multiple sclerosis and Crohn's disease. A crystal structure of the Fab bound to an α4 integrin β-propeller and thigh domain fragment shows that natalizumab recognizes human-mouse differences on the circumference of the β-propeller domain. The epitope is adjacent to but outside of a ligand-binding groove formed at the interface with the β-subunit βI domain and shows no difference in structure when bound to Fab. Competition between Fab and the ligand vascular cell adhesion molecule (VCAM) for binding to cell surface α4β1 shows noncompetitive antagonism. In agreement, VCAM docking models suggest that binding of domain 1 of VCAM to α4-integrins is unimpeded by the Fab, and that bound Fab requires a change in orientation between domains 1 and 2 of VCAM for binding to α4β1. Mapping of species-specific differences onto α4β1 and α4β7 shows that their ligand-binding sites are highly conserved. Skewing away from these conserved regions of the epitopes recognized by current therapeutic function-blocking antibodies has resulted in previously unanticipated mechanisms of action.
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What OpenQuestion holds
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.