ArticleeLife2021
Low-affinity integrin states have faster ligand-binding kinetics than the high-affinity state.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- MERTK coordinates efferocytosis by regulating integrin localization and activation.Journal of cell science · 2026Article
- Beyond MIDAS: AnACS omega · 2026Article
- FCHo2, not talin, enables inside-out activation of integrin ɑvβ5 in curved adhesions.Nature communications · 2026Article
- A guide to building the matrisome interactome: from computational predictions to experimental validation.The FEBS journal · 2026Review
- FCHo2, instead of talin, enables inside-out activation of integrin ɑvβ5 in curved adhesions.bioRxiv : the preprint server for biology · 2025Article
- Human MAdCAM-1 antibodies as targeted immune modulators.Scientific reports · 2025Article
- An RGD motif on SARS-CoV-2 Spike induces TGF-β signaling and downregulates interferon.Journal of virology · 2025Article
- Spatial regulation of mitochondrial membrane potential by α5β1 integrin engagement in collective cell migration.Journal of cell science · 2025Article
- Phagocytosis by the retinal pigment epithelium: New insights into polarized cell mechanics.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Stabilization of adhesions controls F-actin architecture in mechanotransduction.Communications materials · 2025Article
- Advances in mechanotransduction and sonobiology: effects of audible acoustic waves and low-vibration stimulations on mammalian cells.Biophysical reviews · 2024Review
- Actin-driven nanotopography promotes stable integrin adhesion formation in developing tissue.Nature communications · 2024Article
- 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
- An αIIbβ3 monoclonal antibody traps a semiextended conformation and allosterically inhibits large ligand binding.Blood advances · 2024Article
- Low-affinity LFA1-dependent outside-in signaling mediates avidity modulation via the Rabin8-Rab8 axis.PNAS nexus · 2024Article
- Article
- Integrating integrins with the hallmarks of cancer.Matrix biology : journal of the International Society for Matrix Biology · 2024Review
- A Flow Cytometry-Based High-Throughput Technique for Screening Integrin-Inhibitory Drugs.Journal of visualized experiments : JoVE · 2024Article
- Defined extracellular matrix compositions support stiffness-insensitive cell spreading and adhesion signaling.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Integrin conformational ensembles contain two low-affinity states, bent-closed and extended-closed, and an active, high-affinity, extended-open state. It is widely thought that integrins must be activated before they bind ligand; however, one model holds that activation follows ligand binding. As ligand-binding kinetics are not only rate limiting for cell adhesion but also have important implications for the mechanism of activation, we measure them here for integrins α4β1 and α5β1 and show that the low-affinity states bind substantially faster than the high-affinity state. On- and off-rates are similar for integrins on cell surfaces and as ectodomain fragments. Although the extended-open conformation's on-rate is ~20-fold slower, its off-rate is ~25,000-fold slower, resulting in a large affinity increase. The tighter ligand-binding pocket in the open state may slow its on-rate. Low-affinity integrin states not only bind ligand more rapidly, but are also more populous on the cell surface than high-affinity states. Thus, our results suggest that integrin binding to ligand may precede, rather than follow, activation by 'inside-out 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.