Structural basis for adaptation of lactobacilli to gastrointestinal mucus
Structural basis for adaptation of lactobacilli to gastrointestinal mucus
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DOI：
10.1111/1462-2920.12377
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发表时间：
2014-03-01
影响因子：
5.1
通讯作者：
Juge, Nathalie
中科院分区：
文献类型：
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作者：
Etzold, Sabrina;Kober, Olivia I.;Juge, Nathalie
覆盖在胃肠道(GI)上皮的粘液层对于选择和维持与肠道细菌的动态平衡相互作用至关重要。然而，这些相互作用的基础机制尚不清楚。在这里，我们提供了对典型粘液结合蛋白(MUB)的结构和功能的见解，MUB是一种在胃肠道中的乳杆菌中发现的多重复细胞表面粘附素。X射线结晶学和小角X射线散射显示，原子力显微镜显示，珠子呈串状重复排列，产生174 nm长的蛋白质原纤维。每个重复序列由Ig和粘蛋白结合蛋白(MucBP)模块组成。全长MUB通过涉及末端唾液酸化粘蛋白多糖的多种相互作用被限制在粘液中。虽然单个MUB结构域在结构上与革兰氏阳性病原体的菌毛蛋白相似，但MUB的特殊结构为乳杆菌通过最大限度地与粘液受体相互作用、加强细菌在粘液层中的滞留来适应宿主生态位的机制提供了结构上的解释。总之，这项研究揭示了可能影响微生物在粘液和胃肠道中的趋向性的功能和结构特征，为共生菌和益生菌适应黏膜环境的机制提供了独特的见解。
The mucus layer covering the gastrointestinal (GI) epithelium is critical in selecting and maintaining homeostatic interactions with our gut bacteria. However, the underpinning mechanisms of these interactions are not understood. Here, we provide structural and functional insights into the canonical mucus-binding protein (MUB), a multi-repeat cell-surface adhesin found in Lactobacillus inhabitants of the GI tract. X-ray crystallography together with small-angle X-ray scattering demonstrated a beads on a string' arrangement of repeats, generating 174nm long protein fibrils, as shown by atomic force microscopy. Each repeat consists of tandemly arranged Ig- and mucin-binding protein (MucBP) modules. The binding of full-length MUB was confined to mucus via multiple interactions involving terminal sialylated mucin glycans. While individual MUB domains showed structural similarity to fimbrial proteins from Gram-positive pathogens, the particular organization of MUB provides a structural explanation for the mechanisms in which lactobacilli have adapted to their host niche by maximizing interactions with the mucus receptors, potentiating the retention of bacteria within the mucus layer. Together, this study reveals functional and structural features which may affect tropism of microbes across mucus and along the GI tract, providing unique insights into the mechanisms adopted by commensals and probiotics to adapt to the mucosal environment.