Structural characterization of the inflammatory moiety of a variable major lipoprotein of Borrelia recurrentis
Structural characterization of the inflammatory moiety of a variable major lipoprotein of Borrelia recurrentis
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DOI：
10.1074/jbc.275.2.937
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发表时间：
2000-01-14
影响因子：
4.8
通讯作者：
Morris, H
中科院分区：
文献类型：
--
作者：
Scragg, IG;Kwiatkowski, D;Morris, H
由复发伯氏疏螺旋体引起的虱子传播的回归热，提供了肿瘤坏死因子（TNF）在人类严重感染病理中的致病作用的最佳记录之一。我们已经确定了复发伯氏疏螺旋体的主要TNF诱导因子是可变主脂蛋白（Vmp），在这里我们报告了Vmp的完整基因序列，包括其脂蛋白前导序列。使用天然Vmp的代谢标记形式，我们确认TNF诱导特性与分子的脂质部分相关。四极正交飞行时间质谱法明确地定位了天然多肽nh2末端半胱氨酸的脂质部分，并指出存在与C16:0、C16:0、C16:0甘油半胱氨酸结构一致的三种形式；C18:1, C16:0， C16:0甘油半胱氨酸；C18:0, C16:0， C16:0甘油半胱氨酸，这些数据提供了TNF诱导天然伯氏疏螺旋体脂蛋白脂质修饰与大肠杆菌小鼠脂蛋白结构同源的第一个直接证据。
Louse-borne relapsing fever, caused by Borrelia recurrentis, provides one of the best documented examples of the causative role of tumor necrosis factor (TNF) in the pathology of severe infection in humans, We have identified the principal TNF-inducing factor of B. recurrentis as a variable major lipoprotein (Vmp), Here we report the complete gene sequence of Vmp, including its lipoprotein leader sequence. Using metabolically labeled forms of the native Vmp we confirm that the TNF inducing properties are associated with the lipid portion of the molecule. Quadrupole orthogonal time of flight mass spectrometry unequivocally locates the lipidic moiety at the NH2-terminal cysteine of the native polypeptide, and indicates the existence of three forms which are consistent with the structures C16:0, C16:0, C16:0 glyceryl cysteine; C18:1, C16:0, C16:0 glyceryl cysteine; and C18:0, C16:0, C16:0 glyceryl cysteine, These data provide the first direct evidence that the TNF inducing lipid modification of native Borrelia lipoproteins is a structural homologue of the murein lipoprotein of Escherichia coli.