Gray, Declan A, White, Joshua BR, Oluwole, Abraham O, Rath, Parthasarathi, Glenwright, Amy J, Mazur, Adam, Zahn, Michael, Basle, Arnaud, Morland, Carl, Evans, Sasha L et al (show 6 more authors)
(2021)
Insights into SusCD-mediated glycan import by a prominent gut symbiont.
NATURE COMMUNICATIONS, 12 (1).
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Insights into SusCD-mediated glycan import by a prominent gut symbiont.pdf - Published version Download (3MB) | Preview |
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Polysaccharides, Oligosaccharides, Bacterial Proteins, Ligands, Cryoelectron Microscopy, Magnetic Resonance Spectroscopy, Symbiosis, Protein Conformation, Structure-Activity Relationship, Models, Molecular, Gastrointestinal Microbiome |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 08 Apr 2021 10:14 |
| Last Modified: | 18 Jan 2023 22:54 |
| DOI: | 10.1038/s41467-020-20285-y |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3118206 |
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