ArticleProceedings of the National Academy of Sciences of the United States of America2017
Structural basis of kindlin-mediated integrin recognition and activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 161 citations in OpenAlex.
- Structural basis of kindlin-3 in leukocyte adhesion deficiency III.Journal of thrombosis and haemostasis : JTH · 2026Article
- Kindlin-3 sustains cytokine interleukin-2 signaling by linking its receptor to integrin LFA-1.The Journal of biological chemistry · 2026Article
- DHT-Induced lncRNA AC092718.4 Promotes Prostate Cancer Cell Proliferation via ceRNA Mechanism.Genes · 2026Article
- FCHo2, not talin, enables inside-out activation of integrin ɑvβ5 in curved adhesions.Nature communications · 2026Article
- Kindlins regulate integrin- and growth factor-dependent ureteric bud formation.Development (Cambridge, England) · 2026Article
- FCHo2, instead of talin, enables inside-out activation of integrin ɑvβ5 in curved adhesions.bioRxiv : the preprint server for biology · 2025Article
- Kindlin Regulates Mechanosensitive Activation and Adhesion Assembly of Integrin beta6.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Hydrophobicity-Driven Disruption Mechanism in Kindlin-3 Induced by Leukocyte Adhesion Deficiency Mutation.ACS omega · 2025Article
- Focal adhesion in the tumour metastasis: from molecular mechanisms to therapeutic targets.Biomarker research · 2025Review
- Paxillin and Kindlin: Research Progress and Biological Functions.Biomolecules · 2025Review
- Mesenchymal stromal cells promote the formation of lung cancer organoids via Kindlin-2.Stem cell research & therapy · 2025Article
- The USP12/46 deubiquitinases protect integrins from ESCRT-mediated lysosomal degradation.EMBO reports · 2024Article
- Extracellular Matrix Components and Mechanosensing Pathways in Health and Disease.Biomolecules · 2024Review
- Decoding the molecular mechanism of selective autophagy of glycogen mediated by autophagy receptor STBD1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Myosin light chain 6 (Myl6) interacts with kindlin-3 and is required to support integrin αJournal of thrombosis and haemostasis : JTH · 2024Article
- Acetyl-NPKY of integrin-β1 binds KINDLIN2 to control endothelial cell proliferation and junctional integrity.iScience · 2024Article
- Pan-cancer analyses suggest kindlin-associated global mechanochemical alterations.Communications biology · 2024Article
- FERMT1 promotes cell migration and invasion in non-small cell lung cancer via regulating PKP3-mediated activation of p38 MAPK signaling.BMC cancer · 2024Article
- Talin and kindlin use integrin tail allostery and direct binding to activate integrins.Nature structural & molecular biology · 2023Article
- MicroRNAs in Gingival Crevicular Fluid: An Observational Case-Control Study of Differential Expression in Periodontitis.Non-coding RNA · 2023Article
47 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 4 countries.
Funding
Abstract
Kindlins and talins are integrin-binding proteins that are critically involved in integrin activation, an essential process for many fundamental cellular activities including cell-matrix adhesion, migration, and proliferation. As FERM-domain-containing proteins, talins and kindlins, respectively, bind different regions of β-integrin cytoplasmic tails. However, compared with the extensively studied talin, little is known about how kindlins specifically interact with integrins and synergistically enhance their activation by talins. Here, we determined crystal structures of kindlin2 in the apo-form and the β1- and β3-integrin bound forms. The apo-structure shows an overall architecture distinct from talins. The complex structures reveal a unique integrin recognition mode of kindlins, which combines two binding motifs to provide specificity that is essential for integrin activation and signaling. Strikingly, our structures uncover an unexpected dimer formation of kindlins. Interrupting dimer formation impairs kindlin-mediated integrin activation. Collectively, the structural, biochemical, and cellular results provide mechanistic explanations that account for the effects of kindlins on integrin activation as well as for how kindlin mutations found in patients with Kindler syndrome and leukocyte-adhesion deficiency may impact integrin-mediated processes.
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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.