Publication

Article Metrics

Citations


Online attention

Structural and functional insights into oligopeptide acquisition by the RagAB transporter from Porphyromonas gingivalis

DOI: 10.1038/s41564-020-0716-y DOI Help

Authors: Mariusz Madej (Jagiellonian University) , Joshua B. R. White (University of Leeds) , Zuzanna Nowakowska (Jagiellonian University) , Shaun Rawson (University of Leeds) , Carsten Scavenius (University, Aarhus) , Jan J. Enghild (Aarhus University) , Grzegorz P. Bereta (Jagiellonian University) , Karunakar Pothula (Jacobs University Bremen) , Ulrich Kleinekathoefer (Jacobs University Bremen) , Arnaud Basle (Newcastle University) , Neil A. Ranson (University of Leeds) , Jan Potempa (Jagiellonian University; University of Louisville School of Dentistry) , Bert Van Den Berg (Newcastle University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Microbiology , VOL 25

State: Published (Approved)
Published: May 2020
Diamond Proposal Number(s): 13587

Abstract: Porphyromonas gingivalis, an asaccharolytic member of the Bacteroidetes, is a keystone pathogen in human periodontitis that may also contribute to the development of other chronic inflammatory diseases. P. gingivalis utilizes protease-generated peptides derived from extracellular proteins for growth, but how these peptides enter the cell is not clear. Here, we identify RagAB as the outer-membrane importer for these peptides. X-ray crystal structures show that the transporter forms a dimeric RagA2B2 complex, with the RagB substrate-binding surface-anchored lipoprotein forming a closed lid on the RagA TonB-dependent transporter. Cryo-electron microscopy structures reveal the opening of the RagB lid and thus provide direct evidence for a ‘pedal bin’ mechanism of nutrient uptake. Together with mutagenesis, peptide-binding studies and RagAB peptidomics, our work identifies RagAB as a dynamic, selective outer-membrane oligopeptide-acquisition machine that is essential for the efficient utilization of proteinaceous nutrients by P. gingivalis.

Journal Keywords: Bacterial physiology; Bacterial structural biology; Electron microscopy; X-ray crystallography

Diamond Keywords: Bacteria

Subject Areas: Biology and Bio-materials


Instruments: I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography

Discipline Tags:

Life Sciences & Biotech Health & Wellbeing Dentistry Infectious Diseases Pathogens Structural biology

Technical Tags:

Diffraction Macromolecular Crystallography (MX)