Lipoarabinomannans:: characterization of the multiacylated forms of the phosphatidyl-myo-inositol anchor by NMR spectroscopy
Lipoarabinomannans:: characterization of the multiacylated forms of the phosphatidyl-myo-inositol anchor by NMR spectroscopy
复制标题
DOI：
10.1042/0264-6021:3370453
复制
发表时间：
1999-02-01
影响因子：
4.1
通讯作者：
Puzo, G
中科院分区：
文献类型：
--
作者：
Nigou, J;Gilleron, M;Puzo, G
脂阿拉伯甘露聚糖。其表现出广谱免疫活性，成为分枝杆菌包膜的主要抗原。脂阿拉伯甘露聚糖结构基于磷脂酰-肌-肌醇锚，其完整性已被证明对于脂阿拉伯甘露聚糖生物活性至关重要，特别是对于通过CD 1分子呈递给CD 4/CD 8双阴性α β T细胞至关重要。在这份报告中，开发了一种分析方法，用于高分辨率的P-31-NMR分析的天然，即，多酰化，脂阿拉伯甘露聚糖。一维P-31光谱的细胞脂阿拉伯甘露聚糖，从牛分枝杆菌卡介苗，表现出四个P-31共振代表四种类型的脂阿拉伯甘露聚糖。天然分子的二维H-1-P-31异质多量子相关/homopolymerHartmann-Hahn分析表明，这四种类型的脂阿拉伯甘露聚糖在修饰锚的脂肪酸的数量和位置（从1到4）上不同。除了前面描述的三个酰化位点，即甘油的位置1和2以及与肌醇的C-2连接的甘露糖基单元的位置6之外，我们证明了在肌醇的C-3处存在第四个酰化位置。我们在这里报告的第一个结构研究的本地多酰化lipoarabinomannans，建立完整的磷脂酰肌醇锚的结构。我们的研究结果将有助于获得更多的了解脂阿拉伯甘露聚糖歧视的分子基础，在结合过程中的CD 1分子。
Lipoarabinomannans. which exhibit a large spectrum of immunological activities, emerge as the major antigens of mycobacterial envelopes. The lipoarabinomannan structure is based on a phosphatidyl-myo-inositol anchor whose integrity has been shown to be crucial for lipoarabinomannan biological activity and particularly for presentation to CD4/CD8 double-negative alpha beta T cells by CD1 molecules. In this report, an analytical approach was developed for high-resolution P-31-NMR analysis of native, i.e, multiacylated, lipoarabinomannans. The one-dimensional P-31 spectrum of cellular lipoarabinomannans, from Mycobacterium bovis Bacillus Calmette-Guerin, exhibited four P-31 resonances typifying four types of lipoarabinomannans. Two-dimensional H-1-P-31 heteronuclear multiple-quantum-correlation/homonuclear Hartmann-Hahn analysis of the native molecules showed that these four types of lipoarabinomannan differed in the number and localization of fatty acids (from 1 to 4) esterifying the anchor. Besides the three acylation sites previously described, i.e. positions 1 and 2 of glycerol and 6 of the mannosyl unit linked to the C-2 of myo-inositol, we demonstrate the existence of a fourth acylation position at the C-3 of myo-inositol. We report here the first structural study of native multiacylated lipoarabinomannans, establishing the structure of the intact phosphatidyl-myo-inositol anchor. Our findings would help gain more understanding of the molecular basis of lipoarabinomannan discrimination in the binding process to CD1 molecules.