ArticleThe Journal of biological chemistry2014
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.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Structural basis for the differential recognition of integrin αvβ3 by rhodostomin and trimucrin.Communications biology · 2026Article
- Article
- 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
- Development of New Potential Inhibitors of β1 Integrins through In Silico Methods-Screening and Computational Validation.Life (Basel, Switzerland) · 2022Article
- Lung adenocarcinoma-specific three-integrin signature contributes to poor outcomes by metastasis and immune escape pathways.Journal of translational internal medicine · 2021Article
- Discovery of a new class of integrin antibodies for fibrosis.Scientific reports · 2021Article
- Cell adhesion in cancer: Beyond the migration of single cells.The Journal of biological chemistry · 2020Review
- Collective cancer invasion forms an integrin-dependent radioresistant niche.The Journal of experimental medicine · 2020Article
- Flow-induced mechanotransduction in skeletal cells.Biophysical reviews · 2019Review
- Adenovirus Isolated From a Cat Is Related to Human Adenovirus 1.Frontiers in microbiology · 2019Article
- The Therapeutic Antibody LM609 Selectively Inhibits Ligand Binding to Human αStructure (London, England : 1993) · 2017Article
- Integrins as Therapeutic Targets: Successes and Cancers.Cancers · 2017Review
- Activation mechanisms of αVβ3 integrin by binding to fibronectin: A computational study.Protein science : a publication of the Protein Society · 2017Article
- Functional analysis of four single (RGDWL, RGDWM, RGDWP, RGDMN) and two double (RGDNM, RGDMP) mutants: The importance of methionine (M) in the functional potency of recombinant mojastin (r-Moj).Toxicon : official journal of the International Society on Toxinology · 2016Article
- Ligand-induced Epitope Masking: DISSOCIATION OF INTEGRIN α5β1-FIBRONECTIN COMPLEXES ONLY BY MONOCLONAL ANTIBODIES WITH AN ALLOSTERIC MODE OF ACTION.The Journal of biological chemistry · 2016Article
- Structural Basis for Simvastatin Competitive Antagonism of Complement Receptor 3.The Journal of biological chemistry · 2016Article
- Epitopes in α8β1 and other RGD-binding integrins delineate classes of integrin-blocking antibodies and major binding loops in α subunits.Scientific reports · 2015Article
- Article
- The α-subunit regulates stability of the metal ion at the ligand-associated metal ion-binding site in β3 integrins.The Journal of biological chemistry · 2014Article
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Authors and funding
12 authors.
Funding
Abstract
The function-blocking, non-RGD-containing, and primate-specific mouse monoclonal antibody 17E6 binds the αV subfamily of integrins. 17E6 is currently in phase II clinical trials for treating cancer. To elucidate the structural basis of recognition and the molecular mechanism of inhibition, we crystallized αVβ3 ectodomain in complex with the Fab fragment of 17E6. Protein crystals grew in presence of the activating cation Mn(2+). The integrin in the complex and in solution assumed the genuflected conformation. 17E6 Fab bound exclusively to the Propeller domain of the αV subunit. At the core of αV-Fab interface were interactions involving Propeller residues Lys-203 and Gln-145, with the latter accounting for primate specificity. The Propeller residue Asp-150, which normally coordinates Arg of the ligand Arg-Gly-Asp motif, formed contacts with Arg-54 of the Fab that were expected to reduce soluble FN10 binding to cellular αVβ3 complexed with 17E6. This was confirmed in direct binding studies, suggesting that 17E6 is an allosteric inhibitor of αV integrins.
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