Discipline of Chemistry, School of Basic Sciences, Indian Institute of Technology, Indore, Indore, Madhya Pradesh, India.
Discipline of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore (IITI), Madhya Pradesh, India.
J Cell Biochem. 2019 Mar;120(3):3455-3458. doi: 10.1002/jcb.27619. Epub 2018 Sep 22.
Toll/interleukin-1 like receptors (TLRs) are membrane-spanning proteins crucially involved in innate immunity. On activation, the cytoplasmic toll/interleukin-1 receptor (TIR) domains of these receptors undergo homo- or heterodimerization. Brucella sp. are bacterial pathogens that affect the immune system by suppressing the TLR signaling pathway. They enact this by encoding a TIR domain-containing protein, TcpB, which suppresses NF-κB activation and proinflammatory cytokine secretion mediated by TLR4 receptors. TcpB has been shown to target the Mal-mediated pathway to suppress TLR signaling. The recent identification of its mechanism of interference with TLR4 signaling involving Mal prompted us to further study the structural aspects of TcpB binding with TLR4 and Mal. Our triprotein model displays the overall scaffolding role of TcpB in anchoring TLR4 and Mal thereby inhibiting their interaction leading to the attenuation of the TLR4 pathway.
toll/interleukin-1 样受体 (TLRs) 是一种膜结合蛋白，在先天免疫中起着至关重要的作用。在激活过程中，这些受体的细胞质 toll/interleukin-1 受体 (TIR) 结构域发生同源或异源二聚化。布鲁氏菌是一种细菌病原体，通过抑制 TLR 信号通路来影响免疫系统。它们通过编码一个含有 TIR 结构域的蛋白 TcpB 来实现这一点，TcpB 抑制 TLR4 受体介导的 NF-κB 激活和促炎细胞因子分泌。已经表明 TcpB 靶向 Mal 介导的途径来抑制 TLR 信号。最近发现它干扰 TLR4 信号的机制涉及 Mal，这促使我们进一步研究 TcpB 与 TLR4 和 Mal 结合的结构方面。我们的三蛋白模型显示了 TcpB 在锚定 TLR4 和 Mal 方面的总体支架作用，从而抑制它们的相互作用，导致 TLR4 途径的衰减。
