ArticleProceedings of the National Academy of Sciences of the United States of America2001
Locking in alternate conformations of the integrin alphaLbeta2 I domain with disulfide bonds reveals functional relationships among integrin domains.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 187 citations in OpenAlex.
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- A Flow Cytometry-Based High-Throughput Technique for Screening Integrin-Inhibitory Drugs.Journal of visualized experiments : JoVE · 2024Article
- Endothelial CCRL2 induced by disturbed flow promotes atherosclerosis via chemerin-dependent β2 integrin activation in monocytes.Cardiovascular research · 2023Article
- Nexinhib20 Inhibits Neutrophil Adhesion and βJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- Heterotropic roles of divalent cations in the establishment of allostery and affinity maturation of integrin αXβ2.Cell reports · 2022Article
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- Mitofusin-2 regulates leukocyte adhesion and β2 integrin activation.Journal of leukocyte biology · 2022Article
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- Visualization of integrin molecules by fluorescence imaging and techniques.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2021Article
- The Promiscuous Profile of Complement Receptor 3 in Ligand Binding, Immune Modulation, and Pathophysiology.Frontiers in immunology · 2021Review
- Frontline Science: A flexible kink in the transmembrane domain impairs β2 integrin extension and cell arrest from rolling.Journal of leukocyte biology · 2020Article
- Addressing the Compartmentalization of Specific Integrin Heterodimers in Mouse Sperm.International journal of molecular sciences · 2019Article
- A pivotal role for a conserved bulky residue at the α1-helix of the αI integrin domain in ligand binding.The Journal of biological chemistry · 2017Article
- Protective role of cellular prion protein against TNFα-mediated inflammation through TACE α-secretase.Scientific reports · 2017Article
- Neutrophil recruitment limited by high-affinity bent β2 integrin binding ligand in cis.Nature communications · 2016Article
- Relating conformation to function in integrin α5β1.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Allosteric Regulation of E-Cadherin Adhesion.The Journal of biological chemistry · 2015Article
- Structure and dynamics of the integrin LFA-1 I-domain in the inactive state underlie its inside-out/outside-in signaling and allosteric mechanisms.Structure (London, England : 1993) · 2015Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
We used integrin alphaLbeta2 heterodimers containing I domains locked open (active) or closed (inactive) with disulfide bonds to investigate regulatory interactions among domains in integrins. mAbs to the alphaL I domain and beta2 I-like domain inhibit adhesion of wild-type alphaLbeta2 to intercellular adhesion molecule-1. However, with alphaLbeta2 containing a locked open I domain, mAbs to the I domain were subdivided into subsets (i) that did not inhibit, and thus appear to inhibit by favoring the closed conformation, and (ii) that did inhibit, and thus appear to bind to the ligand binding site. Furthermore, alphaLbeta2 containing a locked open I domain was completely resistant to inhibition by mAbs to the beta2 I-like domain, but became fully susceptible to inhibition after disulfide reduction with DTT. This finding suggests that the I-like domain indirectly contributes to ligand binding by regulating opening of the I domain in wild-type alphaLbeta2. Conversely, locking the I domain closed partially restrained conformational change of the I-like domain by Mn(2+), as measured with mAb m24, which we map here to the beta2 I-like domain. By contrast, locking the I domain closed or open did not affect constitutive or Mn(2+)-induced exposure of the KIM127 epitope in the beta2 stalk region. Furthermore, locked open I domains, in alphaLbeta2 complexes or expressed in isolation on the cell surface, bound to intercellular adhesion molecule-1 equivalently in Mg(2+) and Mn(2+). These results suggest that Mn(2+) activates alphaLbeta2 by binding to a site other than the I domain, most likely the I-like domain of beta2.
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