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解析肠道共生菌罗氏菌属 Ruminococcus gnavus 识别唾液酸的特异性和机制。

Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus.

机构信息

Biomolecular Sciences Building, University of St Andrews, St Andrews, KY16 9ST, UK.

Diamond Light Source Ltd, Diamond House, Harwell Science and Innovation Campus, Didcot, OX11 0FA, UK.

出版信息

Nat Commun. 2017 Dec 19;8(1):2196. doi: 10.1038/s41467-017-02109-8.

DOI:10.1038/s41467-017-02109-8
PMID:29259165
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5736709/
Abstract

Ruminococcus gnavus is a human gut symbiont wherein the ability to degrade mucins is mediated by an intramolecular trans-sialidase (RgNanH). RgNanH comprises a GH33 catalytic domain and a sialic acid-binding carbohydrate-binding module (CBM40). Here we used glycan arrays, STD NMR, X-ray crystallography, mutagenesis and binding assays to determine the structure and function of RgNanH_CBM40 (RgCBM40). RgCBM40 displays the canonical CBM40 β-sandwich fold and broad specificity towards sialoglycans with millimolar binding affinity towards α2,3- or α2,6-sialyllactose. RgCBM40 binds to mucus produced by goblet cells and to purified mucins, providing direct evidence for a CBM40 as a novel bacterial mucus adhesin. Bioinformatics data show that RgCBM40 canonical type domains are widespread among Firmicutes. Furthermore, binding of R. gnavus ATCC 29149 to intestinal mucus is sialic acid mediated. Together, this study reveals novel features of CBMs which may contribute to the biogeography of symbiotic bacteria in the gut.

摘要

直肠真杆菌是一种人类肠道共生菌，其黏蛋白降解能力由一种分子内转涎酶（RgNanH）介导。RgNanH 包含 GH33 催化结构域和唾液酸结合糖结合模块（CBM40）。在这里，我们使用聚糖阵列、STD NMR、X 射线晶体学、突变和结合测定来确定 RgNanH_CBM40（RgCBM40）的结构和功能。RgCBM40 显示出典型的 CBM40β-三明治折叠结构，对唾液糖具有广泛的特异性，对α2,3-或α2,6-唾液乳糖的结合亲和力为毫摩尔级。RgCBM40 与杯状细胞产生的粘液和纯化的粘蛋白结合，为 CBM40 作为一种新型细菌粘液黏附素提供了直接证据。生物信息学数据显示，RgCBM40 典型的结构域在厚壁菌门中广泛存在。此外，R. gnavus ATCC 29149 对肠道粘液的结合是通过唾液酸介导的。总之，这项研究揭示了 CBM 的新特征，这可能有助于肠道共生细菌的生物地理学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8236/5736709/6b687549eee4/41467_2017_2109_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8236/5736709/74de40ea9912/41467_2017_2109_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8236/5736709/af2506c0ecc0/41467_2017_2109_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8236/5736709/48f36291362e/41467_2017_2109_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8236/5736709/4798698340b1/41467_2017_2109_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8236/5736709/82a697782f9c/41467_2017_2109_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8236/5736709/290942e7cdd6/41467_2017_2109_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8236/5736709/4876325dd86b/41467_2017_2109_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8236/5736709/6b687549eee4/41467_2017_2109_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8236/5736709/74de40ea9912/41467_2017_2109_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8236/5736709/af2506c0ecc0/41467_2017_2109_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8236/5736709/48f36291362e/41467_2017_2109_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8236/5736709/4798698340b1/41467_2017_2109_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8236/5736709/82a697782f9c/41467_2017_2109_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8236/5736709/290942e7cdd6/41467_2017_2109_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8236/5736709/4876325dd86b/41467_2017_2109_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8236/5736709/6b687549eee4/41467_2017_2109_Fig8_HTML.jpg

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