EMD-10245
Structure of the RagAB peptide importer in the 'open-closed' state
EMD-10245
Single-particle3.3 Å

Map released: 20/05/2020
Last modified: 13/11/2024
Sample Organism:
Porphyromonas gingivalis (strain ATCC BAA-308 / W83)
Sample: RagAB with putative peptide substrate
Fitted models: 6smq (Avg. Q-score: 0.587)
Raw data: EMPIAR-10543
Deposition Authors: White JBR
,
Ranson NA
Sample: RagAB with putative peptide substrate
Fitted models: 6smq (Avg. Q-score: 0.587)
Raw data: EMPIAR-10543
Deposition Authors: White JBR


Structural and functional insights into oligopeptide acquisition by the RagAB transporter from Porphyromonas gingivalis.
Madej M
,
White JBR
,
Nowakowska Z
,
Rawson S
,
Scavenius C
,
Enghild JJ
,
Bereta GP
,
Pothula K,
Kleinekathoefer U
,
Basle A
,
Ranson NA
,
Potempa J
,
van den Berg B
(2020) Nat Microbiol , 5 , 1016 - 1025












(2020) Nat Microbiol , 5 , 1016 - 1025
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.
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.