ArticleProceedings of the National Academy of Sciences of the United States of America2009
Structure of an integrin alphaIIb beta3 transmembrane-cytoplasmic heterocomplex provides insight into integrin activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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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.
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Who cites it
96 citing papers in PubMed, 157 citations in OpenAlex.
- ITGA2B/ITGB3-Related Macrothrombocytopenia Associated With Gain-of-Function Mutations in ITGA2B or ITGB3 Genes.Journal of cellular and molecular medicine · 2026Review
- Full-length αIIbβ3 cryo-EM structure reveals intact integrin initiate-activation intrinsic architecture.Structure (London, England : 1993) · 2024Article
- Development of the Integrated Computer Simulation Model of the Intracellular, Transmembrane, and Extracellular Domain of Platelet Integrin αTH open : companion journal to thrombosis and haemostasis · 2024Article
- Talin and kindlin use integrin tail allostery and direct binding to activate integrins.Nature structural & molecular biology · 2023Article
- Family-wide analysis of integrin structures predicted by AlphaFold2.bioRxiv : the preprint server for biology · 2023Article
- Cryo-EM structures of full-length integrin αIIbβ3 in native lipids.Nature communications · 2023Article
- Molecular basis for the recognition of 24-(S)-hydroxycholesterol by integrin αvβ3.Scientific reports · 2023Article
- Article
- An Updated Review on Glycoprotein IIb/IIIa Inhibitors as Antiplatelet Agents: Basic and Clinical Perspectives.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2023Review
- Review
- Family-wide analysis of integrin structures predicted by AlphaFold2.Computational and structural biotechnology journal · 2023Article
- The structural basis of β2 integrin intra-cellular multi-protein complexes.Biophysical reviews · 2022Review
- The β8 integrin cytoplasmic domain activates extracellular matrix adhesion to promote brain neurovascular development.Development (Cambridge, England) · 2022Article
- Spiers Memorial Lecture: Analysis andFaraday discussions · 2021Article
- Integrin-based mechanosensing through conformational deformation.Biophysical journal · 2021Article
- The MemMoRF database for recognizing disordered protein regions interacting with cellular membranes.Nucleic acids research · 2021Article
- Glanzmann Thrombasthenia: Perspectives from Clinical Practice on Accurate Diagnosis and Optimal Treatment Strategies.Journal of blood medicine · 2021Review
- Chapter 22: Structural and signaling functions of integrins.Biochimica et biophysica acta. Biomembranes · 2020Review
- αIIbβ3 variants in ten families with autosomal dominant macrothrombocytopenia: Expanding the mutational and clinical spectrum.PloS one · 2020Article
- Topological analysis of the gp41 MPER on lipid bilayers relevant to the metastable HIV-1 envelope prefusion state.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Heterodimeric integrin adhesion receptors regulate diverse biological processes including angiogenesis, thrombosis and wound healing. The transmembrane-cytoplasmic domains (TMCDs) of integrins play a critical role in controlling activation of these receptors via an inside-out signaling mechanism, but the precise structural basis remains elusive. Here, we present the solution structure of integrin alphaIIb beta3 TMCD heterodimer, which reveals a right-handed coiled-coil conformation with 2 helices intertwined throughout the transmembrane region. The helices extend into the cytoplasm and form a clasp that differs significantly from a recently published alphaIIb beta3 TMCD structure. We show that while a point mutation in the clasp interface modestly activates alphaIIb beta3, additional mutations in the transmembrane interface have a synergistic effect, leading to extensive integrin activation. Detailed analyses and structural comparison with previous studies suggest that extensive integrin activation is a highly concerted conformational transition process, which involves transmembrane coiled-coil unwinding that is triggered by the membrane-mediated alteration and disengagement of the membrane-proximal clasp. Our results provide atomic insight into a type I transmembrane receptor heterocomplex and the mechanism of integrin inside-out transmembrane signaling.
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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.