Skip to content

Research at St Andrews

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

Research output: Contribution to journalArticle

Author(s)

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, Garry L Taylor, Ajit Varki, Jesus Angulo, Nathalie Juge

School/Research organisations

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.

Close

Details

Original languageEnglish
Article number2196
Number of pages15
JournalNature Communications
Volume8
Early online date19 Dec 2017
DOIs
StateE-pub ahead of print - 19 Dec 2017

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. PRIMA-1Met suppresses colorectal cancer independent of p53 by targeting MEK

    Lu, T., Zou, Y., Xu, G., Potter, J. A., Taylor, G. L., Duan, Q., Yang, Q., Xiong, H., Qiu, H., Ye, D., Zhang, P., Yu, S., Yuan, X., Zhu, F., Wang, Y. & Xiong, H. 27 Oct 2016 In : Oncotarget. 7, 50, p. 83017-83030 14 p.

    Research output: Contribution to journalArticle

  2. Streptococcus pneumoniae NanC. Structural insights into the specificity and mechanism of a sialidase that produces a sialidase inhibitor

    Owen, C. D., Lukacik, P., Potter, J. A., Sleator, O., Taylor, G. L. & Walsh, M. A. 13 Nov 2015 In : Journal of Biological Chemistry. 290, 46, p. 27736-27748 13 p.

    Research output: Contribution to journalArticle

  3. Immunomodulatory Compounds

    Taylor, G. L. & Connaris, H. 30 Jul 2015 A61K31/74

    Research output: Patent

  4. Discovery of intramolecular trans-sialidases in human gut microbiota suggests novel mechanisms of mucosal adaptation

    Tailford, L. E., Owen, C. D., Walshaw, J., Crost, E. H., Hardy-Goddard, J., Le Gall, G., de Vos, W. M., Taylor, G. L. & Juge, N. Jul 2015 In : Nature Communications. 6, 12 p., 7624

    Research output: Contribution to journalArticle

Related by journal

  1. Nature Communications (Journal)

    Gardner, A. (Reviewer)
    Feb 2018

    Activity: Publication peer-review and editorial workPeer review of manuscripts

Related by journal

  1. C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca2+-permeable AMPA receptor-mediated excitotoxicity

    Thangaraj Selvaraj , B. , Livesey , M. , Zhao , C. , Gregory , J. , James, O. , Cleary, E. , Chouhan, A. K. , Gane, A. , Perkins, E. , Dando, O. , Lillico, S. , Lee, Y-B. , Nishimura, A. , Poreci, U. , Thankamony, S. , Pray, M. , Vasistha, N. , Magnani, D. , Borooah, S. , Burr, K. & 12 others Story, D., McCampbell, A., Shaw, C., Kind, P., Aitman, T. J., Whitelaw, B., Wilmut, I., Smith, C., Miles, G. B., Hardingham, G., Wyllie, D. & Chandran, S. 24 Jan 2018 In : Nature Communications. 9, 14 p., 347

    Research output: Contribution to journalArticle

  2. A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage

    Ladds, M. J. G. W. , van Leeuwen, I. M. M. , Drummond, C. J. , Chu, S. , Healy, A. R. , Popova, G. , Pastor-Fernández, A. , Mollick, T. , Darekar, S. , Sedimbi, S. K. , Nekulova, M. , Sachweh, M. C. C. , Campbell, J. , Higgins, M. , Tuck, C. , Popa, M. , Safont, M. M. , Gelebart, P. , Fandalyuk, Z. , Thompson, A. M. & 26 others Svensson, R., Gustavsson, A-L., Johansson, L., Färnegårdh, K., Yngve, U., Saleh, A., Haraldsson, M., D'Hollander, A. C. A., Franco, M., Zhao, Y., Håkansson, M., Walse, B., Larsson, K., Peat, E. M., Pelechano, V., Lunec, J., Vojtesek, B., Carmena, M., Earnshaw, W. C., McCarthy, A. R., Westwood, N. J., Arsenian-Henriksson, M., Lane, D. P., Bhatia, R., McCormack, E. & Laín, S. 16 Mar 2018 In : Nature Communications. 9, 1107

    Research output: Contribution to journalArticle

  3. Anion stabilised hypercloso-hexaalane Al6H6

    Bonyhady, S. J., Collis, D., Holzmann, N., Edwards, A. J., Piltz, R. O., Frenking, G., Stasch, A. & Jones, C. 6 Aug 2018 In : Nature Communications. 9, 6 p., 3079

    Research output: Contribution to journalArticle

  4. Collective magnetism in an artificial 2D XY spin system

    Leo, N., Holenstein, S., Schildknecht, D., Sendetskyi, O., Luetkens, H., Derlet, P. M., Scagnoli, V., Lançon, D., Mardegan, J. R. L., Prokscha, T., Suter, A., Salman, Z., Lee, S. & Heyderman, L. J. 20 Jul 2018 In : Nature Communications. 9, 1, 8 p., 2850

    Research output: Contribution to journalArticle

  5. Crossover from lattice to plasmonic polarons of a spin-polarised electron gas in ferromagnetic EuO

    Riley, J. M., Caruso, F., Verdi, C., Duffy, L., Watson, M. D., Bawden, L., Volckaert, K., van der Laan, G., Hesjedal, T., Hoesch, M., Giustino, F. & King, P. D. 13 Jun 2018 In : Nature Communications. 9, 8 p., 2305

    Research output: Contribution to journalArticle

ID: 251880416