Use of Atomic Force Microscopy to Study the Multi-Modular Interaction of Bacterial Adhesins to Mucins.

Use of Atomic Force Microscopy to Study the Multi-Modular Interaction of Bacterial Adhesins to Mucins.
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DOI:
10.3390/ijms17111854
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发表时间:
2016-11-08
影响因子:
5.6
通讯作者:
Juge N
Juge N
中科院分区:
生物学2区
文献类型:
--
作者:
Gunning AP;Kavanaugh D;Thursby E;Etzold S;MacKenzie DA;Juge N

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覆盖胃肠道(GI)上皮的粘液层在选择和维持与肠道细菌的稳态相互作用方面至关重要。然而,这些相互作用的分子细节还没有很好地理解。在这里,我们提供了机械的见解典型的粘液结合蛋白(MUB),一个大的多重复细胞表面粘附在乳酸杆菌栖息的胃肠道中发现的粘附特性。我们使用原子力显微镜来解开驱动MUB介导的粘蛋白粘附的机制。使用单分子力谱,我们表明,MUB显示出显着的粘附特性,有利于MUB和粘蛋白介导的多个重复构成的粘附素的展开之间的纳米弹簧般的粘附模型。我们获得了MUB自身相互作用的直接证据; MUB-MUB遵循类似的结合模式,证实了MUB模块化结构介导了这种机制。这与半乳糖凝集素-3(Gal-3)所呈现的粘蛋白粘附行为形成鲜明对比,半乳糖凝集素-3(Gal-3)是一种哺乳动物凝集素,其特征在于单个碳水化合物结合结构域(CRD)。本文报道的结合机制与MUB的特定结构组织完美匹配,MUB通过其长且线性的多重复结构最大化与粘蛋白聚糖受体的相互作用,增强细菌在外粘液层内的保留。
The mucus layer covering the gastrointestinal (GI) epithelium is critical in selecting and maintaining homeostatic interactions with our gut bacteria. However, the molecular details of these interactions are not well understood. Here, we provide mechanistic insights into the adhesion properties of the canonical mucus-binding protein (MUB), a large multi-repeat cell–surface adhesin found in Lactobacillus inhabiting the GI tract. We used atomic force microscopy to unravel the mechanism driving MUB-mediated adhesion to mucins. Using single-molecule force spectroscopy we showed that MUB displayed remarkable adhesive properties favouring a nanospring-like adhesion model between MUB and mucin mediated by unfolding of the multiple repeats constituting the adhesin. We obtained direct evidence for MUB self-interaction; MUB–MUB followed a similar binding pattern, confirming that MUB modular structure mediated such mechanism. This was in marked contrast with the mucin adhesion behaviour presented by Galectin-3 (Gal-3), a mammalian lectin characterised by a single carbohydrate binding domain (CRD). The binding mechanisms reported here perfectly match the particular structural organization of MUB, which maximizes interactions with the mucin glycan receptors through its long and linear multi-repeat structure, potentiating the retention of bacteria within the outer mucus layer.
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