2009年3月1日 · The TLR4–MD-2–LPS structure illustrates the remarkable versatility of the ligand recognition mechanisms employed by the TLR family4,5, which is essential for defence against diverse microbial...

2009年3月1日 · Toll 样受体 (TLR) 4 和髓样分化因子 2 (MD-2) 形成异二聚体，可识别结构多样的 LPS 分子中的常见“模式”。 为了了解 TLR4-MD-2-LPS 复合物的配体特异性和受体激活机制，我们确定了其晶体结构。 LPS 结合诱导了 m 形受体多聚体的形成，该多聚体由对称排列的 TLR4-MD-2-LPS 复合物的两个拷贝组成。 LPS 与 MD-2 中的大疏水袋相互作用并直接桥接多聚体的两个组分。 LPS 的 6 条脂质链中有 5 条深埋在口袋内，其余的链暴露在 MD-2 的表面，与 TLR4 的 …

MD2是一种特殊的外分泌蛋白，能帮助TLR4识别LPS。 3种蛋白质（CD14、TLR4和MD2）的不同组合决定了TLR4对不同结构LPS的识别能力，其中跨膜蛋白TLR4起关键作用。 当LPS与TLR4膜外基团结合时，其膜内基团发生构象变化，将信号转到免疫细胞内部。 在细胞内部，激活髓样分化因子88（Myeloid Differentiation factor 88， MyD88）、IL-1R相关蛋白激酶（interleukin recep-tor-associated kinase，IRAK）与IRAK2和肿瘤坏死因子受体活化因子6等信号分子，通过一连串的 …

2009年1月21日 · Toll-like receptor (TLR) 4 and myeloid differentiation factor 2 (MD-2) form a heterodimer that recognizes a common 'pattern' in structurally diverse LPS molecules. To understand the ligand specificity and receptor activation mechanism of the TLR4-MD-2-LPS complex we determined its crystal structure.

2025年1月31日 · Artesunate has been reported to inhibit the Toll-like receptor 4 (TLR4) pathway in macrophages after stimulation with lipopolysaccharide (LPS), which explains artesunate’s protective effect in ...

2009年4月30日 · Toll-like receptor (TLR) 4 and myeloid differentiation factor 2 (MD-2) form a heterodimer that recognizes a common 'pattern' in structurally diverse LPS molecules. To understand the ligand specificity and receptor activation mechanism of the TLR4-MD-2-LPS complex we determined its crystal structure.

2013年12月6日 · In this review, we discuss the reported structures of the TLR4–MD-2 complex, LBP and CD14, and consider their implications for our understanding of TLR4–MD-2 activation in response to...

2023年12月1日 · In this study, we used receptor structure-based VS and biological detection methods to obtain new TLR4/MD2 inhibitors with an anti-inflammatory activity. All the selected compounds were preliminarily evaluated for their anti-inflammatory activity.

2019年10月14日 · The key residues of TLR4 and TLR4* identified by per-residue free energy decomposition (kcal/mol) in the TLR4/TLR4* interface of ligand-free (TLR4-MD2)2 tetramer, lipopolysaccharide (LPS)-bound (TLR4-MD2)2 tetramer, and neoseptin3-bound (TLR4-MD2)2 tetramer complexes.

Toll-like receptor 4 (TLR4) is a mammalian homologue of Drosophila Toll, a leucine-rich repeat molecule that can trigger innate responses against pathogens. The TLR4 gene has recently been shown to be mutated in C3H/HeJ and C57BL/10ScCr mice, both of which are low responders to lipopolysaccharide (LPS). TLR4 may be a long-sought receptor for LPS.