Redefinition of the carbohydrate binding specificity of Helicobacter pylori BabA adhesin.
Redefinition of the carbohydrate binding specificity of Helicobacter pylori BabA adhesin.
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DOI：
10.1074/jbc.m112.387654
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发表时间：
2012-09-14
期刊：
影响因子：
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通讯作者：
Teneberg S
中科院分区：
文献类型：
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作者：
Benktander J;Ångström J;Breimer ME;Teneberg S
背景：BabA黏附素介导幽门螺杆菌与胃上皮的结合。结果：证实了BabA与O型和A型核心链上的决定因子结合。结论：BabA可与1型和4型核心链上的血型决定因子结合。意义：BabA结合特异性的表征对于理解幽门螺杆菌与靶细胞之间的相互作用具有重要意义。某些幽门螺杆菌菌株使用血型抗原结合黏附素（BabA）粘附在人胃上皮上。所有表达baba的幽门螺杆菌菌株都与1型核心链上的O型决定因子结合，即与Lewis b抗原(Fucα2Galβ3(Fucα4)GlcNAc；Leb)和H型1决定因子（Fucα2Galβ3GlcNAc）。最近，BabA菌株被分为仅识别Leb和H型1决定因子的菌株（指定的专业菌株）和同时结合A和B型1决定因子的菌株（指定的通才菌株）。在这里，通过将这些类型的菌株与不同的鞘糖脂结合，进一步探索了通才型和专才型BabA对碳水化合物识别的结构要求。从O型猪的大肠中分离出三种被专家和通才BabA识别的鞘脂，通过质谱和质子核磁共振鉴定为H型五糖基神经酰胺（Fucα2Galβ3GlcNAcβ3Galβ4Glcβ1Cer）、Globo H六糖基神经酰胺（fucα 2galβ 3galac β 3galβ 4glc β 1cer）和三种复合鞘脂（Fucα2Galβ4GlcNAcβ6(Fucα2Galβ3GlcNAcβ3) galβ 3glcnac β 3galβ 4glcnac β 1cer）的混合物。Fucα2Galβ3GlcNAcβ6(Fucα2Galβ3GlcNAcβ3) galβ 3galβ 4glcnac β 1cer和Fucα2Galβ4（Fucα3)GlcNAcβ6(Fucα2Galβ3GlcNAcβ3) galβ 3glcnac β 3galβ 4glcnac β 1cer）。除了这两种菌株与Globo H六糖基神经酰胺结合，即在4型核心链上的血型O决定因素外，通才型菌株与Globo a七糖基神经酰胺（GalNAcα3(Fucα2)Galβ3GalNAcβ3Galα4Galβ4Glcβ1Cer）结合，即在4型核心链上的血型a决定因素。BabA与这两组同工受体的结合是由于H型1和Globo H的末端双糖以及A型1和Globo A的末端三糖的构象相似。
Background: The BabA adhesin mediates binding of Helicobacter pylori to the gastric epithelium. Results: Binding of BabA to blood group O and A determinants on type 4 core chains was demonstrated. Conclusion: The BabA binds to blood group determinants on both type 1 and type 4 core chains. Significance: Characterization of the binding specificities of BabA is important for understanding the interactions between H. pylori and target cells. 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; Leb) and the H type 1 determinant (Fucα2Galβ3GlcNAc). Recently, BabA strains have been categorized into those recognizing only Leb 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.