Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus
| Autor: | Tanja Šuligoj, Serena Monaco, Louise E. Tailford, Xi Chen, Ajit Varki, John Walshaw, Hai Yu, C. David Owen, Romane Lallement, Jesús Angulo, Laura Vaux, Sandra Tribolo, Garry L. Taylor, Zahra Khedri, Andrew Bell, Karine Lecointe, Nathalie Juge, Marc Horrex |
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| Přispěvatelé: | Universidad de Sevilla. Departamento de Química orgánica, University of St Andrews. Office of the Principal, University of St Andrews. School of Biology, University of St Andrews. Biomedical Sciences Research Complex |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
QH301 Biology General Physics and Astronomy Lactose Plasma protein binding Inbred C57BL Crystallography X-Ray Substrate Specificity chemistry.chemical_compound Mice Ruminococcus gnavus Catalytic Domain Ruminococcus Site-Directed QD lcsh:Science Multidisciplinary Crystallography biology Chemistry Bacterial Adhesins 3. Good health Biochemistry Goblet Cells Protein Binding Glycan Colon Science Neuraminidase R Medicine General Biochemistry Genetics and Molecular Biology Article Bacterial genetics Cell Line 03 medical and health sciences QH301 Animals Humans Adhesins Bacterial Symbiosis Glycoproteins 030102 biochemistry & molecular biology Mucin Mucins Computational Biology DAS General Chemistry QD Chemistry Mucus N-Acetylneuraminic Acid Sialic acid Bacterial adhesin Mice Inbred C57BL 030104 developmental biology Mutagenesis biology.protein X-Ray Mutagenesis Site-Directed lcsh:Q |
| Zdroj: | Nature Communications Nature Communications, Vol 8, Iss 1, Pp 1-15 (2017) Nature communications, vol 8, iss 1 idUS. Depósito de Investigación de la Universidad de Sevilla instname idUS: Depósito de Investigación de la Universidad de Sevilla Universidad de Sevilla (US) |
| Popis: | 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. The mucus layer is an important physical niche within the gut which harbours a distinct microbial community. Here the authors show that specific carbohydrate-binding modules associated with bacterial carbohydrate-active enzymes are mucus adhesins that target regions of the distal colon rich in sialomucins. |
| Databáze: | OpenAIRE |
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