ArticleProceedings of the National Academy of Sciences of the United States of America2004
Integrin beta3 regions controlling binding of murine mAb 7E3: implications for the mechanism of integrin alphaIIbbeta3 activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 77 citations in OpenAlex.
- Embedding a commitment to equitable global access into basic and early-phase translational research.Journal of clinical and translational science · 2025Review
- The heparin-binding domain of VEGF165 directly binds to integrin αvβ3 and VEGFR2/KDR D1: a potential mechanism of negative regulation of VEGF165 signaling by αvβ3.Frontiers in cell and developmental biology · 2024Article
- The C-type lectin domain of CD62P (P-selectin) functions as an integrin ligand.Life science alliance · 2023Article
- A specialized integrin-binding motif enables proTGF-β2 activation by integrin αVβ6 but not αVβ8.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Platelet binding to polymerizing fibrin is avidity driven and requires activated αIIbβ3 but not fibrin cross-linking.Blood advances · 2021Article
- Electron microscopy shows that binding of monoclonal antibody PT25-2 primes integrin αIIbβ3 for ligand binding.Blood advances · 2021Article
- Visualization of integrin molecules by fluorescence imaging and techniques.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2021Article
- Dominant role of αIIbβ3 in platelet interactions with cross-linked fibrin fragment D-dimer.Blood advances · 2020Article
- Cryo-Electron Microscopy Structure of the αIIbβ3-Abciximab Complex.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- A Novel αToxins · 2019Article
- Integrin activation by the lipid molecule 25-hydroxycholesterol induces a proinflammatory response.Nature communications · 2019Article
- Probing Membrane Receptor-Ligand Specificity with Surface- and Tip- Enhanced Raman Scattering.Analytical chemistry · 2017Article
- Integrins as Therapeutic Targets: Successes and Cancers.Cancers · 2017Review
- αIIbβ3 binding to a fibrinogen fragment lacking the γ-chain dodecapeptide is activation dependent and EDTA inducible.Blood advances · 2017Article
- Integrin-based therapeutics: biological basis, clinical use and new drugs.Nature reviews. Drug discovery · 2016Review
- Article
- Atomic basis for the species-specific inhibition of αV integrins by monoclonal antibody 17E6 is revealed by the crystal structure of αVβ3 ectodomain-17E6 Fab complex.The Journal of biological chemistry · 2014Article
- Article
- Approach to the diagnosis and management of drug-induced immune thrombocytopenia.Transfusion medicine reviews · 2013Review
- Elevating local concentrations of GPIIb-IIIa antagonists counteracts platelet thrombus stability.Journal of thrombosis and thrombolysis · 2013Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Abciximab, a derivative of the murine mAb 7E3, protects against ischemic complications of percutaneous coronary interventions by inhibiting ligand binding to the alphaIIbbeta3 receptor. In this study we identified regions on integrin beta3 that control 7E3 binding. Murine/human amino acid substitutions were created in two regions of the betaA domain that previous studies found to influence 7E3 binding: the C177-C184 loop and K125-N133. The T182N substitution and a K125Q mutation reduced 7E3 binding to human beta3 in complex with alphaIIb. The introduction of both the human C177-C184 region and human W129 into murine beta3 was necessary and sufficient to permit 7E3 binding to the human alphaIIb/murine beta3 complex. Although we cannot exclude allosteric effects, we propose that 7E3 binds between C177-C184 and W129, which are within 15 A of each other in the crystal structure and close to the beta3 metal ion-dependent adhesion site. We previously demonstrated that 7E3 binds more rapidly to activated than unactivated platelets. Because it has been proposed that alphaIIbbeta3 changes from a bent to an extended conformation upon activation, we hypothesized that 7E3 binds less well to the bent than the extended conformation. In support of this hypothesis we found that 7E3 bound less well to an alphaIIbbeta3 construct locked in a bent conformation, and unlocking the conformation restored 7E3 binding. Thus, our data are consistent with alphaIIbbeta3 existing in variably bent conformations in equilibrium with each other on unactivated platelets, and activation resulting in alphaIIbbeta3 adopting a more extended conformation.
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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.