ArticleBiochemistry2012
α(V)β(3) integrin crystal structures and their functional implications.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed.
- Selective inhibition of platelet inflammatory tether formation via force-modulated vibrational states of integrin αIIbβ3.Journal of molecular modeling · 2026Article
- Structural basis of HPA-1a alloimmunization in FNAIT and allosteric regulation of integrin conformation.Blood · 2026Article
- Structural basis for the differential recognition of integrin αvβ3 by rhodostomin and trimucrin.Communications biology · 2026Article
- Human ITGAV variants are associated with immune dysregulation, brain abnormalities, and colitis.The Journal of experimental medicine · 2024Article
- Recent Applications of In Silico Approaches for Studying Receptor Mutations Associated with Human Pathologies.Molecules (Basel, Switzerland) · 2024Review
- 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
- A large-scale screening identified in USH2A gene the P3272L founder pathogenic variant explaining familial Usher syndrome in Sardinia, Italy.BMC ophthalmology · 2024Article
- Article
- Molecular mechanisms of catch bonds and their implications for platelet hemostasis.Biophysical reviews · 2023Review
- Family-wide analysis of integrin structures predicted by AlphaFold2.bioRxiv : the preprint server for biology · 2023Article
- Review
- Family-wide analysis of integrin structures predicted by AlphaFold2.Computational and structural biotechnology journal · 2023Article
- Use of Ecto-Tagged Integrins to Monitor Integrin Exocytosis and Endocytosis.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Review
- Heterotropic roles of divalent cations in the establishment of allostery and affinity maturation of integrin αXβ2.Cell reports · 2022Article
- Analysis of Integrin αInternational journal of molecular sciences · 2022Article
- Article
- Halting the Spread of Herpes Simplex Virus-1: The Discovery of an Effective Dual αvβ6/αvβ8 Integrin Ligand.Journal of medicinal chemistry · 2021Article
- Structural modeling, mutation analysis, andComputational and structural biotechnology journal · 2020Article
- AvCardiovascular therapeutics · 2020Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Many questions about the significance of structural features of integrin α(V)β(3) with respect to its mechanism of activation remain. We have determined and re-refined crystal structures of the α(V)β(3) ectodomain linked to C-terminal coiled coils (α(V)β(3)-AB) and four transmembrane (TM) residues in each subunit (α(V)β(3)-1TM), respectively. The α(V) and β(3) subunits with four and eight extracellular domains, respectively, are bent at knees between the integrin headpiece and lower legs, and the headpiece has the closed, low-affinity conformation. The structures differ in the occupancy of three metal-binding sites in the βI domain. Occupancy appears to be related to the pH of crystallization, rather than to the physiologic regulation of ligand binding at the central, metal ion-dependent adhesion site. No electron density was observed for TM residues and much of the α(V) linker. α(V)β(3)-AB and α(V)β(3)-1TM demonstrate flexibility in the linker between their extracellular and TM domains, rather than the previously proposed rigid linkage. A previously postulated interface between the α(V) and β(3) subunits at their knees was also not supported, because it lacks high-quality density, required rebuilding in α(V)β(3)-1TM, and differed markedly between α(V)β(3)-1TM and α(V)β(3)-AB. Together with the variation in domain-domain orientation within their bent ectodomains between α(V)β(3)-AB and α(V)β(3)-1TM, these findings are compatible with the requirement for large structural changes, such as extension at the knees and headpiece opening, in conveying activation signals between the extracellular ligand-binding site and the cytoplasm.
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Registered trials
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