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

Nat Microbiol. 2020 Aug;5(8):1016-1025. doi: 10.1038/s41564-020-0716-y. Epub 2020 May 11.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cryoelectron Microscopy
  • Crystallography, X-Ray
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Molecular Dynamics Simulation
  • Oligopeptides / metabolism*
  • Periodontitis / microbiology
  • Porphyromonas gingivalis / genetics
  • Porphyromonas gingivalis / growth & development
  • Porphyromonas gingivalis / metabolism*
  • Protein Conformation


  • Bacterial Proteins
  • Membrane Transport Proteins
  • Oligopeptides
  • RagA protein, Porphyromonas gingivalis
  • RagB protein, bacteria