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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From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [107]
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From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [107]
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From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [107]
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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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Phaser crystallographic software
McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612
Hynes (2002) · doi:10.1016/s0092-8674(02)00971-6 · Cited by 8,606
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MolProbity: all-atom contacts and structure validation for proteins and nucleic acids
Davis, I., Leaver‐Fay, A., Chen, V. B., Block, J. N., Kapral, G. J., Wang, X., Murray, L. W., Arendall, W. B., Snoeyink, J. S., Richardson, J. S., et al. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm216 · Cited by 3,918
International Tables for Crystallography
(2013) · International Tables for Crystallography · doi:10.1107/97809553602060000113 · Cited by 3,833
Shull, M. M., Ormsby, I., Kier, A. B., Pawlowski, S., Diebold, R. J., Yin, M., Allen, R., Sidman, C., Proetzel, G., Calvin, D., et al. (1992) · Nature · doi:10.1038/359693a0 · Cited by 2,985
Munger, J. S., Huang, X., Kawakatsu, H., Griffiths, M. J. D., Dalton, S. L., Wu, J., Pittet, J.-F., Kaminski, N., Garat, C., Matthay, M. A., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80545-0 · Cited by 2,076
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Plow, E. F., Pierschbacher, M. D., Ruoslahti, E. I., Marguerie, G. A., & Ginsberg, M. H. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.23.8057 · Cited by 579
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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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