Molecular Characterization of Lipopolysaccharide Binding to Human α-1-Acid Glycoprotein.
Molecular Characterization of Lipopolysaccharide Binding to Human α-1-Acid Glycoprotein.
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DOI：
10.1155/2012/475153
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发表时间：
2012
影响因子：
5.3
通讯作者：
Velkov T
中科院分区：
文献类型：
--
作者：
Huang JX;Azad MA;Yuriev E;Baker MA;Nation RL;Li J;Cooper MA;Velkov T
AGP结合血浆中循环脂多糖（LPS）的能力被认为有助于降低细菌脂质A分子的促炎作用。在这里，我们第一次表征了来自一些致病性革兰氏阴性细菌的LPS的人AGP结合特征：大肠杆菌、鼠伤寒沙门氏菌、肺炎克雷伯氏菌、铜绿假单胞菌和粘质沙雷氏菌。采用表面等离子体共振（SPR）技术研究了AGP-LPS相互作用的亲和力和构效关系（SAR）。为了剖析LPS的脂质A、核心寡糖和O-抗原多糖组分的贡献，将来自光滑菌株的LPS的AGP结合亲和力与脂质A、Kdo 2-脂质A、Ra、Rd和Re粗糙LPS突变体进行比较。结合数据的SAR分析表明，除了脂A和LPS的核心组分所起的重要作用外，O-抗原多糖的独特的种属和菌株特异性碳水化合物结构主要决定了对AGP的结合亲和力。总之，这些数据与AGP在对入侵的革兰氏阴性菌的急性期炎症反应期间血浆中LPS的结合和转运中的作用一致。
The ability of AGP to bind circulating lipopolysaccharide (LPS) in plasma is believed to help reduce the proinflammatory effect of bacterial lipid A molecules. Here, for the first time we have characterized human AGP binding characteristics of the LPS from a number of pathogenic Gram-negative bacteria: Escherichia coli, Salmonella typhimurium, Klebsiella pneumonia, Pseudomonas aeruginosa, and Serratia marcescens. The binding affinity and structure activity relationships (SAR) of the AGP-LPS interactions were characterized by surface plasma resonance (SPR). In order to dissect the contribution of the lipid A, core oligosaccharide and O-antigen polysaccharide components of LPS, the AGP binding affinity of LPS from smooth strains, were compared to lipid A, Kdo2-lipid A, Ra, Rd, and Re rough LPS mutants. The SAR analysis enabled by the binding data suggested that, in addition to the important role played by the lipid A and core components of LPS, it is predominately the unique species- and strain-specific carbohydrate structure of the O-antigen polysaccharide that largely determines the binding affinity for AGP. Together, these data are consistent with the role of AGP in the binding and transport of LPS in plasma during acute-phase inflammatory responses to invading Gram-negative bacteria.