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P血型组织相关糖鞘脂唾液酸半乳糖基球蛋白作为尿路致病性大肠杆菌的优先结合受体:从人肾中分离及结构表征

The P histo-blood group-related glycosphingolipid sialosyl galactosyl globoside as a preferred binding receptor for uropathogenic Escherichia coli: isolation and structural characterization from human kidney.

作者信息

Stroud M R, Stapleton A E, Levery S B

机构信息

Department of Cell Surface Biochemistry, Northwest Hospital, Seattle, Washington 98125, USA.

出版信息

Biochemistry. 1998 Dec 15;37(50):17420-8. doi: 10.1021/bi9814639.

DOI:10.1021/bi9814639
PMID:9860857
Abstract

The P histo-blood group-related glycosphingolipid, sialosyl galactosyl globoside (SGG), has recently been implicated as a preferred binding receptor for uropathogenic Escherichia coli [Stapleton, A. E., Stroud, M. R., Hakomori, S., and Stamm, W. E. (1998) Infect. Immun. 66, 3856-3861]. We report here the purification and complete structural characterization of SGG from normal human kidney. Using metabolically [35S]-labeled E. coli as a probe, a monosialylated glycosphingolipid was isolated to homogeneity. The glycosphingolipid was purified by a combination of high-performance liquid chromatography and preparative high-performance thin-layer chromatography and its structure unambiguously elucidated by 1H NMR, electrospray ionization mass spectrometry, and methylation analysis. Its primary structure was shown to be identical to a previously characterized, developmentally regulated, globo-series glycolipid thought to be unique to human teratocarcinoma. The significance of this structure as a unique receptor in human kidney for uropathogenic E. coli and its role in the pathogenesis of urinary tract infections are discussed.

摘要

P血型组织血型相关糖鞘脂,唾液酸半乳糖基球蛋白(SGG),最近被认为是尿路致病性大肠杆菌的一种优先结合受体[斯台普顿,A.E.,斯特劳德,M.R.,哈科莫里,S.,和斯塔姆,W.E.(1998年)《感染与免疫》66,3856 - 3861]。我们在此报告从正常人肾脏中纯化并对SGG进行完整的结构表征。使用代谢性[35S]标记的大肠杆菌作为探针,分离出一种单唾液酸化糖鞘脂达到同质。该糖鞘脂通过高效液相色谱和制备型高效薄层色谱相结合的方法进行纯化,其结构通过1H核磁共振、电喷雾电离质谱和甲基化分析明确阐明。其一级结构显示与先前表征的、发育调控的、球系列糖脂相同,该糖脂被认为是人类畸胎癌所特有的。讨论了这种结构作为人肾脏中尿路致病性大肠杆菌的独特受体的意义及其在尿路感染发病机制中的作用。

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