The Toll-like receptor 4 region Glu24-Pro34 is critical for interaction with MD-2.
The Toll-like receptor 4 region Glu24-Pro34 is critical for interaction with MD-2.
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DOI：
10.1016/j.bbrc.2005.01.021
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发表时间：
2005-03
影响因子：
3.1
通讯作者：
C. Nishitani;H. Mitsuzawa;Naoki Hyakushima;H. Sano;N. Matsushima;Y. Kuroki
中科院分区：
文献类型：
--
作者：
C. Nishitani;H. Mitsuzawa;Naoki Hyakushima;H. Sano;N. Matsushima;Y. Kuroki
Toll样受体4（TLR 4）是脂多糖（LPS）的信号传导受体，但需要MD-2（与胞外TLR 4结构域相关的分子）来有效地响应LPS。本研究的目的是确定参与MD-2识别的TLR 4区域的一级序列的临界延伸。TLR 4和TLR 4/2a嵌合体与MD-2共沉淀，但缺失突变体TLR 4 ΔE24-P34不能与MD-2共沉淀。与MD-2结合一致，LPS缀合的珠沉淀TLR 4和TLR 4/2a嵌合体，但不沉淀TLR 2与MD-2。TLR 4 ΔE24-P34几乎不与LPS-珠共沉淀。TLR 4 ΔE24-P34和MD-2共转染的细胞对LPS刺激无NF-κB活化。这些结果清楚地表明Glu 24-Pro34的氨基端TLR 4区域对于MD-2结合和LPS信号传导是关键的。
Toll-like receptor 4 (TLR4) is a signaling receptor for lipopolysaccharide (LPS) but requires MD-2, a molecule associated with the extracellular TLR4 domain, to respond efficiently to LPS. The purpose of this study was to determine the critical stretch of primary sequence in the TLR4 region involved in MD-2 recognition. TLR4 and TLR4/2a chimera consisting of the TLR4 region Met1-Phe54and the TLR2 region Ala53-Ser784were coprecipitated with MD-2, but the deletion mutant TLR4ΔE24-P34in which the TLR4 region Glu24-Pro34was deleted failed to coprecipitate. In agreement with the MD-2 binding, LPS-conjugated beads sedimented TLR4 and TLR4/2a chimera but not TLR2 with MD-2. TLR4ΔE24-P34barely coprecipitated with LPS-beads. The cells that had been cotransfected with TLR4ΔE24-P34and MD-2 did not induce NF-κB activation in response to LPS. These results clearly demonstrate that the amino-terminal TLR4 region of Glu24-Pro34is critical for MD-2 binding and LPS signaling.