NMR spectral mapping of Lipid A molecular patterns affected by interaction with the innate immune receptor CD14.

NMR spectral mapping of Lipid A molecular patterns affected by interaction with the innate immune receptor CD14.
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受先天免疫受体 CD14 相互作用影响的脂质 A 分子模式的 NMR 谱图。

DOI:
10.1016/j.bbrc.2008.11.113
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发表时间:
2009
影响因子:
3.1
通讯作者:
Jain,NitinU
Jain,NitinU
中科院分区:
生物学4区
文献类型:
--
作者:
Albright,Seth;Agrawal,Prashansa;Jain,NitinU

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可溶性CD 14(sCD 14)是一种血清糖蛋白,作为对细菌内毒素的先天免疫应答的一部分,以高亲和力与脂多糖(LPS)的脂质A部分结合。为了研究脂质A与sCD 14的结构相互作用,我们制备了一种同位素标记形式的完全活性和化学定义的内毒素,Kdo 2-脂质A,这使我们能够对与sCD 14结合的这种激动剂配体进行详细的NMR光谱映射,并首次鉴定在与sCD 14形成复合物期间受到强烈影响的结构区域。这些映射到两个相邻的区域,包括糖头基的下部和酰基链I、III和V的上半部分,它们在空间上接近1-和4′-磷酸末端。此外,我们首次检测到受影响共振的微分动力学行为的存在,表明动力学在sCD 14识别脂质A模式的机制中可能起作用。
Soluble CD14 (sCD14) is a serum glycoprotein that binds to the Lipid A moiety of lipopolysaccharides (LPS) with high affinity as part of the innate immune response to bacterial endotoxins. In order to investigate structural interactions of Lipid A with sCD14, we have prepared an isotopically labeled form of a fully active and chemically defined endotoxin, Kdo2–Lipid A, which allowed us to carry out detailed NMR spectral mapping of this agonist ligand bound to sCD14 and identify for the first time structural regions that are strongly affected during complex formation with sCD14. These map to two adjacent areas comprising the lower portions of the sugar headgroup and upper half of the acyl chains I, III, and V, which are spatially proximal to the 1- and 4′-phosphate ends. Additionally, we have detected for the first time, presence of differential dynamic behavior for the affected resonances, suggesting a likely role for dynamics in the mechanism of Lipid A pattern recognition by sCD14.
DOI: 10.1016/1074-7613(94)90093-0
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