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

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. Robinson, Sebastian Hiller, Neil A. Ranson, David N. Bolam*, Bert Van den berg

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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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.
Original languageEnglish
Article number44
Number of pages14
JournalNature Communications
Volume12
DOIs
Publication statusPublished - 4 Jan 2021

Keywords

  • X-ray crystallography
  • Transporters
  • Cryoelectron microscopy
  • Bacteriology
  • UKRI
  • BBSRC
  • BB/P003192/1
  • MRC
  • MR/N020413/1

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