Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology, P. O. Box 440, University of Gothenburg, S-405 30 Göteborg, Sweden.
J Biol Chem. 2012 Sep 14;287(38):31712-24. doi: 10.1074/jbc.M112.387654. Epub 2012 Jul 20.
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.
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。