Year: 2021
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,560
Funders: National Science Foundation, Wellcome Trust, Diamond Light Source, Research Councils UK, Academy of Medical Sciences, University of Leeds, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Directorate for Biological Sciences, Medical Research Council, Biotechnology and Biological Sciences Research Council, National Center of Competence in Research Materials’ Revolution: Computational Design and Discovery of Novel Materials
Awards: G1708749397, The molecular mechanism of outer membrane protein insertion by BamA and its role as a target for novel antibiotics, G399966401, Applications of Mass Spectrometry to Membrane Protein Drug Development, Elucidating the mechanism of transport and regulation of the Mep ammonium transporters using cryo-electron microscopy, G4370759242, Modern Cryo-Electron Microscopy with Direct Electron Detection at the University of Leeds., G4854761912, Elucidating the mechanism of transport and regulation of the Mep ammonium transporters using cryo-electron microscopy, G540949950, G6582298172, Language in Space: The Cartographic Representation of Dialects, G6868616705, Modern Cryo-Electron Microscopy with Direct Electron Detection at the University of Leeds., G8414415875, Structural basis for nutrient acquisition by dominant members of the gut microbiota, G8718757983
OpenAlex ID: W3120964251