Enzyme and Protein Chemistry, Department of Systems Biology, Technical University of Denmark, Søltofts Plads, Building 224, DK-2800, Kgs. Lyngby, Denmark.
Mol Microbiol. 2013 Dec;90(5):1100-12. doi: 10.1111/mmi.12419. Epub 2013 Oct 31.
Glycan utilization plays a key role in modulating the composition of the gut microbiota, but molecular insight into oligosaccharide uptake by this microbial community is lacking. Arabinoxylo-oligosaccharides (AXOS) are abundant in the diet, and are selectively fermented by probiotic bifidobacteria in the colon. Here we show how selectivity for AXOS uptake is established by the probiotic strain Bifidobacterium animalis subsp. lactis Bl-04. The binding protein BlAXBP, which is associated with an ATP-binding cassette (ABC) transporter that mediates the uptake of AXOS, displays an exceptionally broad specificity for arabinosyl-decorated and undecorated xylo-oligosaccharides, with preference for tri- and tetra-saccharides. Crystal structures of BlAXBP in complex with four different ligands revealed the basis for this versatility. Uniquely, the protein was able to recognize oligosaccharides in two opposite orientations, which facilitates the optimization of interactions with the various ligands. Broad substrate specificity was further enhanced by a spacious binding pocket accommodating decorations at different mainchain positions and conformational flexibility of a lid-like loop. Phylogenetic and genetic analyses show that BlAXBP is highly conserved within Bifidobacterium, but is lacking in other gut microbiota members. These data indicate niche adaptation within Bifidobacterium and highlight the metabolic syntrophy (cross-feeding) among the gut microbiota.
糖利用在调节肠道微生物群落组成方面起着关键作用，但对于该微生物群落中寡糖摄取的分子机制仍知之甚少。阿拉伯木聚糖寡糖（AXOS）在饮食中含量丰富，并被结肠中的益生菌双歧杆菌选择性发酵。在这里，我们展示了益生菌菌株 Bifidobacterium animalis subsp. lactis Bl-04 如何建立对 AXOS 摄取的选择性。与介导 AXOS 摄取的 ATP 结合盒（ABC）转运体相关的结合蛋白 BlAXBP 对阿拉伯糖基修饰和未修饰的木寡糖表现出异常广泛的特异性，偏爱三糖和四糖。与四种不同配体结合的 BlAXBP 的晶体结构揭示了这种多功能性的基础。独特的是，该蛋白能够以两种相反的取向识别寡糖，这有助于优化与各种配体的相互作用。宽阔的结合口袋能够容纳不同主链位置的修饰，并允许盖子样环的构象灵活性，进一步增强了广泛的底物特异性。系统发育和遗传分析表明，BlAXBP 在双歧杆菌中高度保守，但在其他肠道微生物群成员中缺失。这些数据表明双歧杆菌内的生态位适应，并强调了肠道微生物群之间的代谢共生（交叉喂养）。
