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重新定义幽门螺杆菌 BabA 黏附素的碳水化合物结合特异性。

Redefinition of the carbohydrate binding specificity of Helicobacter pylori BabA adhesin.

机构信息

Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology, P. O. Box 440, University of Gothenburg, S-405 30 Göteborg, Sweden.

出版信息

J Biol Chem. 2012 Sep 14;287(38):31712-24. doi: 10.1074/jbc.M112.387654. Epub 2012 Jul 20.

DOI:10.1074/jbc.M112.387654
PMID:22822069
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3442506/
Abstract

Certain Helicobacter pylori strains adhere to the human gastric epithelium using the blood group antigen-binding adhesin (BabA). All BabA-expressing H. pylori strains bind to the blood group O determinants on type 1 core chains, i.e. to the Lewis b antigen (Fucα2Galβ3(Fucα4)GlcNAc; Le(b)) and the H type 1 determinant (Fucα2Galβ3GlcNAc). Recently, BabA strains have been categorized into those recognizing only Le(b) and H type 1 determinants (designated specialist strains) and those that also bind to A and B type 1 determinants (designated generalist strains). Here, the structural requirements for carbohydrate recognition by generalist and specialist BabA were further explored by binding of these types of strains to a panel of different glycosphingolipids. Three glycosphingolipids recognized by both specialist and generalist BabA were isolated from the small intestine of a blood group O pig and characterized by mass spectrometry and proton NMR as H type 1 pentaglycosylceramide (Fucα2Galβ3GlcNAcβ3Galβ4Glcβ1Cer), Globo H hexaglycosylceramide (Fucα2Galβ3GalNAcβ3Galα4Galβ4Glcβ1Cer), and a mixture of three complex glycosphingolipids (Fucα2Galβ4GlcNAcβ6(Fucα2Galβ3GlcNAcβ3)Galβ3GlcNAcβ3Galβ4Glcβ1Cer, Fucα2Galβ3GlcNAcβ6(Fucα2Galβ3GlcNAcβ3)Galβ3GlcNAcβ3Galβ4Glcβ1Cer, and Fucα2Galβ4(Fucα3)GlcNAcβ6(Fucα2Galβ3GlcNAcβ3)Galβ3GlcNAcβ3Galβ4Glcβ1Cer). In addition to the binding of both strains to the Globo H hexaglycosylceramide, i.e. a blood group O determinant on a type 4 core chain, the generalist strain bound to the Globo A heptaglycosylceramide (GalNAcα3(Fucα2)Galβ3GalNAcβ3Galα4Galβ4Glcβ1Cer), i.e. a blood group A determinant on a type 4 core chain. The binding of BabA to the two sets of isoreceptors is due to conformational similarities of the terminal disaccharides of H type 1 and Globo H and of the terminal trisaccharides of A type 1 and Globo A.

摘要

某些幽门螺杆菌菌株使用血型抗原结合黏附素(BabA)附着在人类胃上皮细胞上。所有表达 BabA 的幽门螺杆菌菌株都与 1 型核心链上的血型 O 决定簇结合,即与 Lewis b 抗原(Fucα2Galβ3(Fucα4)GlcNAc;Le(b))和 H 型 1 决定簇(Fucα2Galβ3GlcNAc)结合。最近,BabA 菌株已被分为仅识别 Le(b)和 H 型 1 决定簇的菌株(指定的专家菌株)和也与 A 和 B 型 1 决定簇结合的菌株(指定的通用型菌株)。在这里,通过这些类型的菌株与一组不同的糖脂的结合,进一步探讨了通用型和专家型 BabA 对碳水化合物识别的结构要求。从小肠中分离出三种被专家型和通用型 BabA 识别的糖脂,并通过质谱和质子 NMR 鉴定为 H 型 1 五糖神经酰胺(Fucα2Galβ3GlcNAcβ3Galβ4Glcβ1Cer)、Globo H 六糖神经酰胺(Fucα2Galβ3GalNAcβ3Galα4Galβ4Glcβ1Cer)和三种复杂糖脂的混合物(Fucα2Galβ4GlcNAcβ6(Fucα2Galβ3GlcNAcβ3)Galβ3GlcNAcβ3Galβ4Glcβ1Cer、Fucα2Galβ3GlcNAcβ6(Fucα2Galβ3GlcNAcβ3)Galβ3GlcNAcβ3Galβ4Glcβ1Cer 和 Fucα2Galβ4(Fucα3)GlcNAcβ6(Fucα2Galβ3GlcNAcβ3)Galβ3GlcNAcβ3Galβ4Glcβ1Cer)。除了两种菌株与 Globo H 六糖神经酰胺(即 4 型核心链上的 O 型血型决定簇)的结合外,通用型菌株还与 Globo A 七糖神经酰胺(GalNAcα3(Fucα2)Galβ3GalNAcβ3Galα4Galβ4Glcβ1Cer)结合,即 4 型核心链上的 A 型血型决定簇。BabA 与这两组同受体的结合是由于 H 型 1 和 Globo H 的末端二糖以及 A 型 1 和 Globo A 的末端三糖的构象相似。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03e/3442506/94a0f815542c/zbc0391222890010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03e/3442506/5577cd63deb1/zbc0391222890001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03e/3442506/0d6a45076486/zbc0391222890004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03e/3442506/48ebeaa2d3a2/zbc0391222890006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03e/3442506/2337a17f4424/zbc0391222890007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03e/3442506/4640cc2708fc/zbc0391222890008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03e/3442506/b46649eceb52/zbc0391222890009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03e/3442506/94a0f815542c/zbc0391222890010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03e/3442506/5577cd63deb1/zbc0391222890001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03e/3442506/543c8ed52a91/zbc0391222890002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03e/3442506/0d6a45076486/zbc0391222890004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03e/3442506/fbf0db00cd56/zbc0391222890005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03e/3442506/48ebeaa2d3a2/zbc0391222890006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03e/3442506/2337a17f4424/zbc0391222890007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03e/3442506/4640cc2708fc/zbc0391222890008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03e/3442506/b46649eceb52/zbc0391222890009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b03e/3442506/94a0f815542c/zbc0391222890010.jpg

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