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Carsten Scavenius

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

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  • Mariusz Madej, Jagiellonian University
  • ,
  • Joshua B. R. White, University of Leeds
  • ,
  • Zuzanna Nowakowska, Jagiellonian University
  • ,
  • Shaun Rawson, University of Leeds
  • ,
  • Carsten Scavenius
  • Jan J. Enghild
  • 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, University of Leeds
  • ,
  • Bert van den Berg, Newcastle University

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 RagA(2)B(2) 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.

Porphyromonas gingivalis, an oral anaerobe involved in the pathogenesis of periodontitis, relies on extracellular proteases to degrade proteins into peptides for growth, but how these peptides enter the cell is unknown. Here, the authors identify RagAB as the outer-membrane importer for these peptides and solve its structure, elucidating that it works via a 'pedal bin' mechanism of nutrient uptake.

Original languageEnglish
JournalNature Microbiology
Pages (from-to)1016-1025
Number of pages10
Publication statusPublished - Aug 2020

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