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

C. David Owen; Louise E. Tailford; Serena Monaco; Tanja Šuligoj; Laura Vaux; Romane  Lallement; Zahra Khedri; Hai Yu; Karine Lecointe; John Walshaw; Sandra Tribolo; Marc  Horrex; Andrew Bell; Xi Chen; Gary L. Taylor; Ajit Varki; Jesus Angulo; Nathalie Juge

doi:10.1038/s41467-017-02109-8

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

C. David Owen, Louise E. Tailford, Serena Monaco, Tanja Šuligoj, Laura Vaux, Romane Lallement, Zahra Khedri, Hai Yu, Karine Lecointe, John Walshaw, Sandra Tribolo, Marc Horrex, Andrew Bell, Xi Chen, Gary L. Taylor, Ajit Varki, Jesus Angulo, Nathalie Juge

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Abstract

Ruminococcus gnavus is a human gut symbiont which 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 b-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.

Original language	English
Article number	2196
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/s41467-017-02109-8
Publication status	Published - 19 Dec 2017

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Accepted ManuscriptAccepted author manuscript, 2.94 MBLicence: CC BY
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Jesus Angulo
- J.Angulouea.acuk
- School of Chemistry, Pharmacy and Pharmacology - Honorary Senior Lecturer
- Pharmaceutical Materials and Soft Matter - Member
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Owen, C. D., Tailford, L. E., Monaco, S., Šuligoj, T., Vaux, L., Lallement, R., Khedri, Z., Yu, H., Lecointe, K., Walshaw, J., Tribolo, S., Horrex, M., Bell, A., Chen, X., Taylor, G. L., Varki, A., Angulo, J., & Juge, N. (2017). Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus. Nature Communications, 8, [2196]. https://doi.org/10.1038/s41467-017-02109-8

Owen, C. David ; Tailford, Louise E. ; Monaco, Serena ; Šuligoj, Tanja ; Vaux, Laura ; Lallement, Romane ; Khedri, Zahra ; Yu, Hai ; Lecointe, Karine ; Walshaw, John ; Tribolo, Sandra ; Horrex, Marc ; Bell, Andrew ; Chen, Xi ; Taylor, Gary L. ; Varki, Ajit ; Angulo, Jesus ; Juge, Nathalie. / Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus. In: Nature Communications. 2017 ; Vol. 8.

@article{719c2962364f425da9e1f8e5a132825d,

title = "Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus",

abstract = "Ruminococcus gnavus is a human gut symbiont which 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 b-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.",

author = "Owen, {C. David} and Tailford, {Louise E.} and Serena Monaco and Tanja {\v S}uligoj and Laura Vaux and Romane Lallement and Zahra Khedri and Hai Yu and Karine Lecointe and John Walshaw and Sandra Tribolo and Marc Horrex and Andrew Bell and Xi Chen and Taylor, {Gary L.} and Ajit Varki and Jesus Angulo and Nathalie Juge",

year = "2017",

month = dec,

day = "19",

doi = "10.1038/s41467-017-02109-8",

language = "English",

volume = "8",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

Owen, CD, Tailford, LE, Monaco, S, Šuligoj, T, Vaux, L, Lallement, R, Khedri, Z, Yu, H, Lecointe, K, Walshaw, J, Tribolo, S, Horrex, M, Bell, A, Chen, X, Taylor, GL, Varki, A, Angulo, J & Juge, N 2017, 'Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus', Nature Communications, vol. 8, 2196. https://doi.org/10.1038/s41467-017-02109-8

Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus. / Owen, C. David; Tailford, Louise E.; Monaco, Serena; Šuligoj, Tanja; Vaux, Laura; Lallement, Romane ; Khedri, Zahra; Yu, Hai; Lecointe, Karine; Walshaw, John; Tribolo, Sandra; Horrex, Marc ; Bell, Andrew; Chen, Xi; Taylor, Gary L.; Varki, Ajit; Angulo, Jesus; Juge, Nathalie.

In: Nature Communications, Vol. 8, 2196, 19.12.2017.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Unravelling the specificity and mechanism of sialic acid recognition by the gut symbiont Ruminococcus gnavus

AU - Owen, C. David

AU - Tailford, Louise E.

AU - Monaco, Serena

AU - Šuligoj, Tanja

AU - Vaux, Laura

AU - Lallement, Romane

AU - Khedri, Zahra

AU - Yu, Hai

AU - Lecointe, Karine

AU - Walshaw, John

AU - Tribolo, Sandra

AU - Horrex, Marc

AU - Bell, Andrew

AU - Chen, Xi

AU - Taylor, Gary L.

AU - Varki, Ajit

AU - Angulo, Jesus

AU - Juge, Nathalie

PY - 2017/12/19

Y1 - 2017/12/19

N2 - Ruminococcus gnavus is a human gut symbiont which 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 b-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.

AB - Ruminococcus gnavus is a human gut symbiont which 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 b-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.

U2 - 10.1038/s41467-017-02109-8

DO - 10.1038/s41467-017-02109-8

M3 - Article

VL - 8

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 2196

ER -

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

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Jesus Angulo

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