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Insights into SusCD-mediated glycan import by a prominent gut symbiont

Author

Listed:
  • Declan A. Gray

    (Newcastle University)

  • Joshua B. R. White

    (University of Leeds)

  • Abraham O. Oluwole

    (University of Oxford)

  • Parthasarathi Rath

    (University of Basel)

  • Amy J. Glenwright

    (Newcastle University)

  • Adam Mazur

    (University of Basel)

  • Michael Zahn

    (University of Basel)

  • Arnaud Baslé

    (Newcastle University)

  • Carl Morland

    (Newcastle University)

  • Sasha L. Evans

    (University of Leeds)

  • Alan Cartmell

    (University of Liverpool)

  • Carol V. Robinson

    (University of Oxford)

  • Sebastian Hiller

    (University of Basel)

  • Neil A. Ranson

    (University of Leeds)

  • David N. Bolam

    (Newcastle University)

  • Bert van den Berg

    (Newcastle University)

Abstract

In Bacteroidetes, one of the dominant phyla of the mammalian gut, active uptake of large nutrients across the outer membrane is mediated by SusCD protein complexes via a “pedal bin” transport mechanism. However, many features of SusCD function in glycan uptake remain unclear, including ligand binding, the role of the SusD lid and the size limit for substrate transport. Here we characterise the β2,6 fructo-oligosaccharide (FOS) importing SusCD from Bacteroides thetaiotaomicron (Bt1762-Bt1763) to shed light on SusCD function. Co-crystal structures reveal residues involved in glycan recognition and suggest that the large binding cavity can accommodate several substrate molecules, each up to ~2.5 kDa in size, a finding supported by native mass spectrometry and isothermal titration calorimetry. Mutational studies in vivo provide functional insights into the key structural features of the SusCD apparatus and cryo-EM of the intact dimeric SusCD complex reveals several distinct states of the transporter, directly visualising the dynamics of the pedal bin transport mechanism.

Suggested Citation

  • Declan A. Gray & Joshua B. R. White & Abraham O. Oluwole & Parthasarathi Rath & Amy J. Glenwright & Adam Mazur & Michael Zahn & Arnaud Baslé & Carl Morland & Sasha L. Evans & Alan Cartmell & Carol V. , 2021. "Insights into SusCD-mediated glycan import by a prominent gut symbiont," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20285-y
    DOI: 10.1038/s41467-020-20285-y
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    Cited by:

    1. Jennifer L. Modesto & Victoria H. Pearce & Guy E. Townsend, 2023. "Harnessing gut microbes for glycan detection and quantification," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Javier Abellon-Ruiz & Kalyanashis Jana & Augustinas Silale & Andrew M. Frey & Arnaud Baslé & Matthias Trost & Ulrich Kleinekathöfer & Bert Berg, 2023. "BtuB TonB-dependent transporters and BtuG surface lipoproteins form stable complexes for vitamin B12 uptake in gut Bacteroides," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Yolanda Y. Huang & Morgan N. Price & Allison Hung & Omree Gal-Oz & Surya Tripathi & Christopher W. Smith & Davian Ho & Héloïse Carion & Adam M. Deutschbauer & Adam P. Arkin, 2024. "Barcoded overexpression screens in gut Bacteroidales identify genes with roles in carbon utilization and stress resistance," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Diego E. Sastre & Nazneen Sultana & Marcos V. A. S. Navarro & Maros Huliciak & Jonathan Du & Javier O. Cifuente & Maria Flowers & Xu Liu & Pete Lollar & Beatriz Trastoy & Marcelo E. Guerin & Eric J. S, 2024. "Human gut microbes express functionally distinct endoglycosidases to metabolize the same N-glycan substrate," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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