布鲁氏菌 TIR 样蛋白 TcpB 与 MyD88 的死亡结构域相互作用。
The Brucella TIR-like protein TcpB interacts with the death domain of MyD88.
机构信息
Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
出版信息
Biochem Biophys Res Commun. 2012 Jan 6;417(1):299-304. doi: 10.1016/j.bbrc.2011.11.104. Epub 2011 Nov 29.
Abstract
The pathogen Brucella melitensis secretes a Toll/interleukin-1 receptor (TIR) domain containing protein that abrogates host innate immune responses. In this study, we have characterized the biochemical interactions of Brucella TIR-like protein TcpB with host innate immune adaptor proteins. Using protein-fragment complementation assays based on Gaussia luciferase and green fluorescent protein, we find that TcpB interacts directly with MyD88 and that this interaction is significantly stronger than the interaction of TcpB with TIRAP, the only other adaptor protein that detectably interacts with TcpB. Surprisingly, the TcpB-MyD88 interaction depends on the death domain (DD) of MyD88, and TcpB does not interact with the isolated TIR domain of MyD88. TcpB disrupts MyD88(DD)-MyD88(DD), MyD88(DD)-MyD88(TIR) and MyD88(DD)-MyD88 interactions but not MyD88-MyD88 or MyD88(TIR)-MyD88(TIR) interactions. Structural models consistent with these results suggest how TcpB might inhibit TLR signaling by targeting MyD88 via a DD-TIR domain interface.
摘要
贝氏疏螺旋体分泌一种包含 Toll/白细胞介素-1 受体（TIR）结构域的蛋白，该蛋白能阻断宿主固有免疫应答。在本研究中，我们对布鲁氏菌 TIR 样蛋白 TcpB 与宿主固有免疫接头蛋白的生化相互作用进行了表征。我们利用基于海肾荧光素酶和绿色荧光蛋白的蛋白片段互补测定法发现，TcpB 与 MyD88 直接相互作用，并且这种相互作用明显强于 TcpB 与唯一能与 TcpB 检测到相互作用的接头蛋白 TIRAP 的相互作用。令人惊讶的是，TcpB-MyD88 相互作用依赖于 MyD88 的死亡结构域（DD），并且 TcpB 不与 MyD88 的分离 TIR 结构域相互作用。TcpB 破坏了 MyD88(DD)-MyD88(DD)、MyD88(DD)-MyD88(TIR)和 MyD88(DD)-MyD88 相互作用，但不破坏 MyD88-MyD88 或 MyD88(TIR)-MyD88(TIR)相互作用。与这些结果一致的结构模型表明，TcpB 如何通过靶向 MyD88 的 DD-TIR 结构域界面来抑制 TLR 信号。
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