Taxanes inhibit human TLR4 signaling by binding to MD-2
LPS is the primary ligand of Toll-like receptor 4, activating it through binding to its accessory protein MD-2. Murine but not human cells expressing MD-2/TLR4 are also activated by paclitaxel. Paclitaxel binds to human MD-2. The binding site of paclitaxel overlaps with the binding site of bis-ANS a...
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Veröffentlicht in: | FEBS letters 2008-11, Vol.582 (28), p.3929-3934 |
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Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | LPS is the primary ligand of Toll-like receptor 4, activating it through binding to its accessory protein MD-2. Murine but not human cells expressing MD-2/TLR4 are also activated by paclitaxel. Paclitaxel binds to human MD-2. The binding site of paclitaxel overlaps with the binding site of bis-ANS and LPS, which results in the ability of taxanes to inhibit LPS signaling in the system with human receptors. Circular dichroic spectra of human MD-2 indicated differences in the chemical environment in the presence of paclitaxel and docetaxel. Molecular docking identified the interacting residues of MD-2 and suggests that hydrophobic interactions govern the binding, while the C-3′N group where the paclitaxel and docetaxel differ is exposed on the surface of MD-2. |
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ISSN: | 0014-5793 1873-3468 |
DOI: | 10.1016/j.febslet.2008.10.037 |