Structural biology of the LPS recognition
Structural biology of the LPS recognition
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DOI：
10.1016/j.ijmm.2007.04.001
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发表时间：
2007-09-01
影响因子：
4.1
通讯作者：
Jerala, Roman
中科院分区：
文献类型：
--
作者：
Jerala, Roman
细菌内毒素（脂多糖- LPS）作为免疫系统最有效的诱导剂之一被细胞外“模式识别受体”的复杂级联识别，所述模式识别受体将LPS从细菌膜陪伴至跨膜受体TLR 4。最近的结构，生物化学和生理学的研究已经推进了我们对受体识别的分子模式的理解。先天免疫系统识别LPS的机制包括LPS结合蛋白（LBP）与LPS结合的第一步，这导致LPS聚集体的破坏。LBP末端的阳离子氨基酸残基起着最重要的作用。LBP的羧基末端结构域与CD 14或细胞膜相互作用，是精简LPS信号传导所必需的。单体CD 14：LPS复合物是可溶的，因为脂质A的酰基链通过与CD 14的疏水口袋相互作用而在很大程度上受到保护而不受溶剂的影响。CD 14不具有LBP和MD-2所特有的强阳离子簇。除了脂质A，CD 14还识别LPS的碳水化合物链，并且沿着LBP控制TLR 4的MyD 88非依赖性信号传导途径的激活。LPS的最终细胞受体是MD-2，其包含强阳离子和疏水结合位点。MD-2结合LPS单体，并且对脂质A部分的酰化模式敏感。MD-2：LPS复合物与Toll样受体4（TLR 4）的胞外域的缔合最终通过胞内TIR结构域的缔合来转导信号，募集衔接蛋白，触发信号级联。(c)2007年，Elsevier GmbH。All rights reserved.
Bacterial endotoxin (lipopolysaccharide - LPS) as one of the most potent inducers of the immune system is recognized by a complex cascade of extracellular "pattern recognition receptors", which chaperone the LPS from the bacterial membrane to the transmembrane receptor TLR4. Recent structural, biochemical and physiological investigations have advanced our understanding of the molecular pattern recognized by the receptors. The proposed mechanism of LPS recognition by the innate immune system involves as the first step binding of the LPS-binding protein (LBP) to LPS, which leads to a disruption of LPS aggregates Cationic amino acid residues at the tip of LBP play the most important role. The carboxyl-terminal domain of LBP, which interacts with CD14 or with the cell membrane, is required to streamline LPS signalling. The monomeric CD14:LPS complex is Soluble, as the acyl chains of the lipid A are to a large extent protected from the solvent by interaction with the hydrophobic pocket of CD14. CD14 does not have a strong cationic cluster, characteristic of LBP and MD-2. Besides lipid A, CD14 recognizes also the carbohydrate chains of LPS and along with LBP governs the activation of the MyD88-independent signalling pathway of TLR4. The final cellular acceptor for LPS is MD-2, which comprises both a strong cationic and a hydrophobic binding site. MD-2 binds the LPS monomer and is sensitive to the acylation pattern of the lipid A moiety. Association of the MD-2:LPS complex to the ectodomain of Toll-like receptor 4 (TLR4) finally transduces the signal through the association of intracellular TIR domain, recruiting the adapter proteins triggering the signalling cascade. (c) 2007 Elsevier GmbH. All rights reserved.