ArticleNature structural & molecular biology2014
Structural basis for pure antagonism of integrin αVβ3 by a high-affinity form of fibronectin.
Article in Nature structural & molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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.
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Who cites it
74 citing papers in PubMed, 129 citations in OpenAlex.
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- The exosomal miRNA/FOXN3 axis empowers fibroblasts with tumor-promoting functions via enhanced migration and altered secretome.Journal of nanobiotechnology · 2026Article
- Exosomal integrin αvβ3 derived from colorectal cancer promotes the liver pre-metastatic niche formation by inducing cancer-associated fibroblasts activation.Clinical and experimental medicine · 2026Article
- Structural basis for the differential recognition of integrin αvβ3 by rhodostomin and trimucrin.Communications biology · 2026Article
- Beyond MIDAS: AnACS omega · 2026Article
- Therapeutic Effect of a Recombinant Human Fibronectin Construct in Skeletal Muscle Repair and Oxidative Stress.International journal of molecular sciences · 2025Article
- Differential tropisms of old and new world hantaviruses influence virulence and developing host-directed antiviral candidates.PLoS pathogens · 2025Article
- In Silico Prediction of Tetrastatin-Derived Peptide Interactions with αvβ3 and α5β1 Integrins.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Review
- A Novel KGD-Based αIIbβ3 Antagonist Prevents Arterial Thrombosis While Preserving Hemostasis and Avoiding Thrombocytopenia.International journal of molecular sciences · 2025Article
- Crystal structure of Isthmin-1 and reassessment of its functional role in pre-adipocyte signaling.Nature communications · 2025Article
- Focal adhesion in the tumour metastasis: from molecular mechanisms to therapeutic targets.Biomarker research · 2025Review
- Switching Roles─Exploring Concentration-Dependent Agonistic versus Antagonistic Behavior of Integrin Ligands.Journal of medicinal chemistry · 2025Article
- Glioblastoma Cell Migration, Invasion and Vasculogenic Mimicry Downmodulated by Novel uPAcyclin Derivatives.Cells · 2025Article
- Interaction of integrin αFrontiers in cell and developmental biology · 2025Article
- The Integrin Receptors: From Discovery to Structure to Medicines.Immunological reviews · 2025Review
- Facile Peptide Macrocyclization and Multifunctionalization via Cyclen Installation.Small methods · 2024Article
- Platelet integrin αIIbβ3 plays a key role in a venous thrombogenesis mouse model.Nature communications · 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
- Conjecturing about Small-Molecule Agonists and Antagonists of α4β1 Integrin: From Mechanistic Insight to Potential Therapeutic Applications.Biomedicines · 2024Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Integrins are important therapeutic targets. However, current RGD-based anti-integrin drugs are also partial agonists, inducing conformational changes that trigger potentially fatal immune reactions and paradoxical cell adhesion. Here we describe the first crystal structure of αVβ3 bound to a physiologic ligand, the tenth type III RGD domain of wild-type fibronectin (wtFN10), or to a high-affinity mutant (hFN10) shown here to act as a pure antagonist. Comparison of these structures revealed a central π-π interaction between Trp1496 in the RGD-containing loop of hFN10 and Tyr122 of the β3 subunit that blocked conformational changes triggered by wtFN10 and trapped hFN10-bound αVβ3 in an inactive conformation. Removing the Trp1496 or Tyr122 side chains or reorienting Trp1496 away from Tyr122 converted hFN10 into a partial agonist. These findings offer new insights into the mechanism of integrin activation and a basis for the design of RGD-based pure antagonists.
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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.