The DOI matches its Crossref record; 39 of the 40 references it cites were found in a registry or an index.
Structural determinants of integrin β-subunit specificity for latent TGF-β
Open accessAbstract
Eight integrin α-β heterodimers recognize ligands with an Arg-Gly-Asp (RGD) motif. However, the structural mechanism by which integrins differentiate among extracellular proteins with RGD motifs is not understood. Here, crystal structures, mutations and peptide-affinity measurements show that αVβ6 binds with high affinity to a RGDLXXL/I motif within the prodomains of TGF-β1 and TGF-β3. The LXXL/I motif forms an amphipathic α-helix that binds in a hydrophobic pocket in the β6 subunit. Elucidation of the basis for ligand binding specificity by the integrin β subunit reveals contributions by three different βI-domain loops, which we designate specificity-determining loops (SDLs) 1, 2 and 3. Variation in a pair of single key residues in SDL1 and SDL3 correlates with the variation of the entire β subunit in integrin evolution, thus suggesting a paradigmatic role in overall β-subunit function.
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In the citing paper
“highlighting context dependency of the various αv-containing integrins in the regulation of fibrosis across different organs”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [107]
In the citing paper
“whereas global loss of β3, β5 or β6 integrins or conditional loss of β8 integrins in myofibroblasts did not”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [107]
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“Pharmacological blockade of αv-containing integrins by a small molecule (CWHM 12) attenuated both liver and lung fibrosis, even when fibrosis was already established107”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [107]
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“Using Pdgfrβ-Cre mice to deplete αv integrins on hepatic myofibroblasts protected mice from carbon tetrachloride-induced hepatic fibrosis”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [107]
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“depletion of the αv integrin subunit on mesenchymal cells has also proven effective in inhibiting fibrosis in models of liver, lung and kidney fibrosis107”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [107]
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Metadata
- Authors
- Dong, X., Hudson, N. E., Lu, C., & Springer, T. A.
- Affiliations
- Boston Children's Hospital (US)
- Corresponding author
- Springer, Timothy A
- Venue
- Nature Structural & Molecular Biology
- Published
- 2014-11-10
- Volume
- 21
- Issue
- 12
- Pages
- 1091-1096
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- PMC
- PMC4717663
- OpenAlex
- W2017269651
- Cited by
- 141
- References
- 40
- Citations by year
- 2026: 11 · 2025: 8 · 2024: 13 · 2023: 13 · 2022: 8 · 2021: 14 · 2020: 17 · 2019: 13 · 2018: 9 · 2017: 17 · 2016: 10 · 2015: 8
- FWCI
- 8.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P01HL103526)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- integrin αvβ6, latent TGF-beta1, RGD motif, ligand specificity, amphipathic helix, hydrophobic pocket
- MeSH terms
- Amino Acid Sequence, Antigens, Neoplasm, Binding Sites, Humans, Models, Molecular, Molecular Sequence Data, Mutation, Integrins, Sequence Alignment, Crystallography, X-Ray, Transforming Growth Factor beta1, Transforming Growth Factor beta3, Protein Interaction Domains and Motifs, HEK293 Cells
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