ArticleNature2011
Basic amino-acid side chains regulate transmembrane integrin signalling.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 74 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
74 citing papers in PubMed.
- Sweetening the bonds: how O-GlcNAcylation modulates cell adhesion.Acta pharmacologica Sinica · 2026Review
- Integrins in cancer: insights into mechanisms and therapeutic potential.Cell communication and signaling : CCS · 2026Review
- Functional unfolding of the integrin αX transmembrane helix.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Integrin Alpha8 Beta1 (81): An In-Depth Review of an Overlooked RGD-Binding Receptor.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2025Article
- Review
- Producing highly effective extracellular vesicles using IBAR and talin F3 domain fusion.Animal cells and systems · 2024Article
- Intrinsic self-organization of integrin nanoclusters within focal adhesions is required for cellular mechanotransduction.bioRxiv : the preprint server for biology · 2023Article
- Targeting integrin pathways: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2023Review
- Review
- The binding of autotaxin to integrins mediates hyperhomocysteinemia-potentiated platelet activation and thrombosis in mice and humans.Blood advances · 2022Article
- The Connection Between Rap1 and Talin1 in the Activation of Integrins in Blood Cells.Frontiers in cell and developmental biology · 2022Review
- Insight Into Pathological Integrin αIIbβ3 Activation From Safeguarding The Inactive State.Journal of molecular biology · 2021Article
- Visualization of integrin molecules by fluorescence imaging and techniques.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2021Article
- Cancer Biology of the Endoplasmic Reticulum Lectin Chaperones Calreticulin, Calnexin and PDIA3/ERp57.Progress in molecular and subcellular biology · 2021Review
- The Activation and Regulation of β2 Integrins in Phagocytes and Phagocytosis.Frontiers in immunology · 2021Review
- Structure and Dynamics of GPCRs in Lipid Membranes: Physical Principles and Experimental Approaches.Molecules (Basel, Switzerland) · 2020Review
- Roles of Membrane Domains in Integrin-Mediated Cell Adhesion.International journal of molecular sciences · 2020Review
- Topological Adaptation of Transmembrane Domains to the Force-Modulated Lipid Bilayer Is a Basis of Sensing Mechanical Force.Current biology : CB · 2020Article
- Chapter 22: Structural and signaling functions of integrins.Biochimica et biophysica acta. Biomembranes · 2020Review
- Biological Machine Learning Combined withMicroorganisms · 2020Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
6 authors.
Funding
Abstract
Side chains of Lys/Arg near transmembrane domain (TMD) membrane-water interfaces can 'snorkel', placing their positive charge near negatively charged phospholipid head groups; however, snorkelling's functional effects are obscure. Integrin β TMDs have such conserved basic amino acids. Here we use NMR spectroscopy to show that integrin β(3)(Lys 716) helps determine β(3) TMD topography. The α(ΙΙb)β(3) TMD structure indicates that precise β(3) TMD crossing angles enable the assembly of outer and inner membrane 'clasps' that hold the αβ TMD together to limit transmembrane signalling. Mutation of β(3)(Lys 716) caused dissociation of α(ΙΙb)β(3) TMDs and integrin activation. To confirm that altered topography of β(3)(Lys 716) mutants activated α(ΙΙb)β(3), we used directed evolution of β(3)(K716A) to identify substitutions restoring default state. Introduction of Pro(711) at the midpoint of β(3) TMD (A711P) increased α(ΙΙb)β(3) TMD association and inactivated integrin α(ΙΙb)β(3)(A711P,K716A). β(3)(Pro 711) introduced a TMD kink of 30 ± 1° precisely at the border of the outer and inner membrane clasps, thereby decoupling the tilt between these segments. Thus, widely occurring snorkelling residues in TMDs can help maintain TMD topography and membrane-embedding, thereby regulating transmembrane signalling.
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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.