Ligand-independent oligomerization of TLR4 regulated by a short hydrophobic region adjacent to the transmembrane domain
Ligand-independent oligomerization of TLR4 regulated by a short hydrophobic region adjacent to the transmembrane domain
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DOI：
10.1016/j.bbrc.2006.01.074
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发表时间：
2006-03-24
影响因子：
3.1
通讯作者：
Miwa, S
中科院分区：
文献类型：
--
作者：
Nishiya, T;Kajita, E;Miwa, S
Toll样受体是激活针对病原体的免疫反应的关键受体。在已鉴定的10多个TLRs中，TLR4是最独特的，因为它与多种配体识别和信号转导的适配器分子结合。然而，TLR4的独特特性和结构特征之间的关系尚不清楚。在这项研究中，我们展示了TLR4的一种新的生化特性。在免疫印迹中观察到TLR4，而不是其他TLRs以高度聚集的形式出现。有趣的是，TLR4的跨膜区和细胞质结构域被其他TLR的跨膜区和细胞质结构域取代，完全取消了TLR4的聚集。此外，我们还发现TLR4的跨膜区附近有一个短的疏水区(HR)；缺少HR的TLR4突变体没有聚集，对脂多糖没有反应。这些结果表明，HR可能在TLR4的功能性齐聚中起关键作用。(C)2006 Elsevier Inc.保留所有权利。
Toll-like receptors (TLRs) are key receptors for the activation of immune responses directed against pathogens. Among the more than 10 identified TLRs, TLR4 is the most unique because it associates with a variety of adaptor molecules for ligand recognition and signal transduction. However, the relationship between the unique characteristics and structural features of TLR4 is poorly defined. In this study, we demonstrate a novel biochemical characteristic of TLR4. TLR4, but not other TLRs, was observed as highly aggregated forms in immunoblotting. Interestingly, substitution of the transmembrane and cytoplasmic domain of TLR4 with those of other TLRs completely abolished the aggregation of TLR4. Furthermore, we found a short hydrophobic region (HR) adjacent to the transmembrane domain of TLR4; the TLR4 mutant lacking the HR was not aggregated and was nonfunctional in response to lipopolysaccharide. These results suggest that the HR may play a critical role in the functional oligomerization of TLR4. (c) 2006 Elsevier Inc. All rights reserved.