ArticleProceedings of the National Academy of Sciences of the United States of America2000
NMR and mutagenesis evidence for an I domain allosteric site that regulates lymphocyte function-associated antigen 1 ligand binding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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52 citing papers in PubMed, 163 citations in OpenAlex.
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- Directing cell delivery to murine atherosclerotic aortic lesions via targeting inflamed circulatory interface using nanocarriers.Frontiers in cardiovascular medicine · 2025Article
- Carbohydrate ligand engagement with CD11b enhances differentiation of tumor-associated myeloid cells for immunotherapy of solid cancers.Journal for immunotherapy of cancer · 2023Article
- A Genetic Model of Constitutively Active Integrin CD11b/CD18.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Structural basis of the leukocyte integrin Mac-1 I-domain interactions with the platelet glycoprotein Ib.Blood advances · 2019Article
- Ligand- and cation-induced structural alterations of the leukocyte integrin LFA-1.The Journal of biological chemistry · 2018Article
- Structural Immunology of Complement Receptors 3 and 4.Frontiers in immunology · 2018Review
- Integrin α2β1 in nonactivated conformation can induce focal adhesion kinase signaling.Scientific reports · 2017Article
- A Functional Analysis on the Interspecies Interaction between Mouse LFA-1 and Human Intercellular Adhesion Molecule-1 at the Cell Level.Frontiers in immunology · 2017Article
- Intrinsic local destabilization of the C-terminus predisposes integrin α1 I domain to a conformational switch induced by collagen binding.Protein science : a publication of the Protein Society · 2016Article
- Structural basis of blocking integrin activation and deactivation for anti-inflammation.Journal of biomedical science · 2015Review
- An internal ligand-bound, metastable state of a leukocyte integrin, αXβ2.The Journal of cell biology · 2013Article
- Virus-mimetic polyplex particles for systemic and inflammation-specific targeted delivery of large genetic contents.Gene therapy · 2013Article
- Small molecule agonists of integrin CD11b/CD18 do not induce global conformational changes and are significantly better than activating antibodies in reducing vascular injury.Biochimica et biophysica acta · 2013Article
- Impact of mutations on the allosteric conformational equilibrium.Journal of molecular biology · 2013Article
- Isoflurane binds and stabilizes a closed conformation of the leukocyte function-associated antigen-1.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2012Article
- Dynamic structural changes are observed upon collagen and metal ion binding to the integrin α1 I domain.The Journal of biological chemistry · 2012Article
- Neutrophil arrest by LFA-1 activation.Frontiers in immunology · 2012Article
- Astroglial integrins in the development and regulation of neurovascular units.Pain research and treatment · 2012Article
- The C-terminal αI domain linker as a critical structural element in the conformational activation of αI integrins.The Journal of biological chemistry · 2011Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The leukocyte integrin, lymphocyte function-associated antigen 1 (LFA-1) (CD11a/CD18), mediates cell adhesion and signaling in inflammatory and immune responses. To support these functions, LFA-1 must convert from a resting to an activated state that avidly binds its ligands such as intercellular adhesion molecule 1 (ICAM-1). Biochemical and x-ray studies of the Mac-1 (CD11b/CD18) I domain suggest that integrin activation could involve a conformational change of the C-terminal alpha-helix. We report the use of NMR spectroscopy to identify CD11a I domain residues whose resonances are affected by binding to ICAM-1. We observed two distinct sites in the CD11a I domain that were affected. As expected from previous mutagenesis studies, a cluster of residues localized around the metal ion-dependent adhesion site (MIDAS) was severely perturbed on ICAM-1 binding. A second cluster of residues distal to the MIDAS that included the C-terminal alpha-helix of the CD11a I domain was also affected. Substitution of residues in the core of this second I domain site resulted in constitutively active LFA-1 binding to ICAM-1. Binding data indicates that none of the 20 substitution mutants we tested at this second site form an essential ICAM-1 binding interface. We also demonstrate that residues in the I domain linker sequences can regulate LFA-1 binding. These results indicate that LFA-1 binding to ICAM-1 is regulated by an I domain allosteric site (IDAS) and that this site is structurally linked to the MIDAS.
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