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Physical contact between lipopolysaccharide and Toll-like receptor 4 revealed by genetic complementation
Open accessAbstract
Some mammalian species show an ability to discriminate between different lipopolysaccharide (LPS) partial structures (for example, lipid A and its congener LA-14-PP, which lacks secondary acyl chains), whereas others do not. Using a novel genetic complementation system involving the transduction of immortalized macrophages from genetically unresponsive C3H/HeJ mice, we now have shown that the species-dependent discrimination between intact LPS and tetra-acyl LPS partial structures is fully attributable to the species origin of Toll-like receptor 4 (Tlr4), an essential membrane-spanning component of the mammalian LPS sensor. Because Tlr4 interprets the chemical structure of an LPS molecule, we conclude that LPS must achieve close physical proximity with Tlr4 in the course of signal transduction.
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Cited by
Janeway, C. A., & Medzhitov, R. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.083001.084359 · Cited by 8,394
Takeda, K., Kaisho, T., & Akira, S. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141126 · Cited by 6,143
Toll-like receptors: critical proteins linking innate and acquired immunity
Akira, S., Takeda, K., & Kaisho, T. (2001) · Nature Immunology · doi:10.1038/90609 · Cited by 4,777
Raetz, C. R. H., & Whitfield, C. (2002) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.71.110601.135414 · Cited by 4,404
Toll-like receptors and innate immunity
Medzhitov, R. (2001) · Nature Reviews Immunology · doi:10.1038/35100529 · Cited by 4,308
Metadata
- Authors
- Poltorak, A., Ricciardi-Castagnoli, P., Citterio, S., & Beutler, B.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2000-02-18
- Volume
- 97
- Issue
- 5
- Pages
- 2163-2167
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2019737761
- Cited by
- 429
- References
- 0
- FWCI
- 19.80
- Type
- journal article
- Language
- en
- Open access
- green
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- Poltorak, A., Ricciardi-Castagnoli, P., Citterio, S., & Beutler, B. (2000). Physical contact between lipopolysaccharide and Toll-like receptor 4 revealed by genetic complementation. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.040565397
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