ArticleThe Journal of biological chemistry2009
Structural determinants of integrin binding to the talin rod.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 93 citations in OpenAlex.
- Optimization of stapled peptide inhibitors reveals design principles for targeting talin-induced integrin activation.bioRxiv : the preprint server for biology · 2026Article
- The Life of a Kidney Podocyte.Acta physiologica (Oxford, England) · 2025Review
- Mechanical Load-Induced Upregulation of Talin2 through Non-Canonical Deubiquitination of OTUB1 Drives Facet Joint Osteoarthritis Pathogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A Review of Talin- and Integrin-Dependent Molecular Mechanisms in Cancer Invasion and Metastasis.International journal of molecular sciences · 2025Review
- Exploring focal adhesion data: dynamic parameter extraction from FRAP and FLAP experiments using chemical master equation.Frontiers in molecular biosciences · 2025Article
- Talin-1 variants associated with spontaneous coronary artery dissection (SCAD) highlight how even subtle changes in multi-functional scaffold proteins can manifest in disease.Human molecular genetics · 2024Article
- High-resolution snapshots of the talin auto-inhibitory states suggest roles in cell adhesion and signaling.Nature communications · 2024Article
- Calpain Promotes LPS-induced Lung Endothelial Barrier Dysfunction via Cleavage of Talin.American journal of respiratory cell and molecular biology · 2023Article
- Intrinsic self-organization of integrin nanoclusters within focal adhesions is required for cellular mechanotransduction.bioRxiv : the preprint server for biology · 2023Article
- Tensin3 interaction with talin drives the formation of fibronectin-associated fibrillar adhesions.The Journal of cell biology · 2022Article
- The structural basis of β2 integrin intra-cellular multi-protein complexes.Biophysical reviews · 2022Review
- Integrin Regulators in Neutrophils.Cells · 2022Review
- New insights into the phosphorylation of the threonine motif of the β1 integrin cytoplasmic domain.Life science alliance · 2022Article
- Talin in mechanotransduction and mechanomemory at a glance.Journal of cell science · 2021Article
- An efficient alpha helix model and simulation framework for stationary electrostatic interaction force estimation.Scientific reports · 2021Article
- Cancer associated talin point mutations disorganise cell adhesion and migration.Scientific reports · 2021Article
- PPM1F controls integrin activity via a conserved phospho-switch.The Journal of cell biology · 2020Article
- A distinct talin2 structure directs isoform specificity in cell adhesion.The Journal of biological chemistry · 2020Article
- Rare Missense Variants in TLN1 Are Associated With Familial and Sporadic Spontaneous Coronary Artery Dissection.Circulation. Genomic and precision medicine · 2019Article
- Pulmonary Endothelial Mechanical Sensing and Signaling, a Story of Focal Adhesions and Integrins in Ventilator Induced Lung Injury.Frontiers in physiology · 2019Review
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 3 countries.
Funding
Abstract
The adaptor protein talin serves both to activate the integrin family of cell adhesion molecules and to couple integrins to the actin cytoskeleton. Integrin activation has been shown to involve binding of the talin FERM domain to membrane proximal sequences in the cytoplasmic domain of the integrin beta-subunit. However, a second integrin-binding site (IBS2) has been identified near the C-terminal end of the talin rod. Here we report the crystal structure of IBS2 (residues 1974-2293), which comprises two five-helix bundles, "IBS2-A" (1974-2139) and "IBS2-B" (2140-2293), connected by a continuous helix with a distinct kink at its center that is stabilized by side-chain H-bonding. Solution studies using small angle x-ray scattering and NMR point to a fairly flexible quaternary organization. Using pull-down and enzyme-linked immunosorbent assays, we demonstrate that integrin binding requires both IBS2 domains, as does binding to acidic phospholipids and robust targeting to focal adhesions. We have defined the membrane proximal region of the integrin cytoplasmic domain as the major binding region, although more membrane distal regions are also required for strong binding. Alanine-scanning mutagenesis points to an important electrostatic component to binding. Thermal unfolding experiments show that integrin binding induces conformational changes in the IBS2 module, which we speculate are linked to vinculin and membrane binding.
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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.