ArticleThe Journal of biological chemistry2009
Integrin activation dynamics between the RGD-binding site and the headpiece hinge.
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 32 papers.
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Who cites it
32 citing papers in PubMed.
- Advances in mechanotransduction and sonobiology: effects of audible acoustic waves and low-vibration stimulations on mammalian cells.Biophysical reviews · 2024Review
- Contributions of the individual domains of αCytoskeleton (Hoboken, N.J.) · 2024Article
- Multiscale models of integrins and cellular adhesions.Current opinion in structural biology · 2023Review
- Review
- Thy-1 (CD90)-regulated cell adhesion and migration of mesenchymal cells: insights into adhesomes, mechanical forces, and signaling pathways.Frontiers in cell and developmental biology · 2023Review
- Review
- Fuzzy binding model of molecular interactions between tropoelastin and integrin alphaVbeta3.Biophysical journal · 2021Article
- With an Ear Up against the Wall: An Update on Mechanoperception inPlants (Basel, Switzerland) · 2021Review
- Article
- When Stiffness Matters: Mechanosensing in Heart Development and Disease.Frontiers in cell and developmental biology · 2020Review
- Integrins as biomechanical sensors of the microenvironment.Nature reviews. Molecular cell biology · 2019Review
- The human platelet antigen-1b (ProThe Journal of biological chemistry · 2018Article
- Receptor-mediated cell mechanosensing.Molecular biology of the cell · 2017Review
- Activation mechanisms of αVβ3 integrin by binding to fibronectin: A computational study.Protein science : a publication of the Protein Society · 2017Article
- Article
- High Affinity vs. Native Fibronectin in the Modulation of αvβ3 Integrin Conformational Dynamics: Insights from Computational Analyses and Implications for Molecular Design.PLoS computational biology · 2017Article
- Structurally governed cell mechanotransduction through multiscale modeling.Scientific reports · 2015Article
- Evolving insights in cell-matrix interactions: elucidating how non-soluble properties of the extracellular niche direct stem cell fate.Acta biomaterialia · 2015Review
- Structural and mechanical functions of integrins.Biophysical reviews · 2014Review
- Mechanical regulation of T-cell functions.Immunological reviews · 2013Review
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Integrins form mechanical links between the extracellular matrix and the cytoskeleton. Although integrin activation is known to be regulated by an allosteric conformational change, which can be induced from the extracellular or intracellular end of the molecule, little is known regarding the sequence of structural events by which signals propagate between distant sites. Here, we reveal with molecular dynamics simulations of the FnIII(10)-bound alpha(V)beta(3) integrin headpiece how the binding pocket and interdomain betaA/hybrid domain hinge on the distal end of the betaA domain are allosterically linked via a hydrophobic T-junction between the middle of the alpha1 helix and top of the alpha7 helix. The key results of this study are: 1) that this T-junction is induced by ligand binding and hinge opening, and thus displays bidirectionality; 2) that formation of this junction can be accelerated by ligand-mediated force; and 3) how formation of this junction is inhibited by Ca(2+) in place of Mg(2+) at the site adjacent to the metal ion-dependent adhesion site ("ADMIDAS"). Together with recent experimental evidence that integrin complexes can form catch bonds (i.e. become strengthened under force), as well as earlier evidence that Ca(2+) at the ADMIDAS results in lower binding affinity, these simulations provide a common structural model for the dynamic process by which integrins become activated.
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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.