Dynamic oligopeptide acquisition by the RagAB transporter from Porphyromonas gingivalis

Madej, M.; White, J.; Nowakowska, Z.; Rawson, S.; Scavenius, C.; Enghild, J.; Bereta, G.; Pothula, K.; Kleinekathoefer, U.; Basle, A.; Ranson, N.; Potempa, J.; van den Berg, B.

doi:10.1101/755678

bioRxiv · 10.1101/755678

Dynamic oligopeptide acquisition by the RagAB transporter from Porphyromonas gingivalis

Madej, M.·White, J.·Nowakowska, Z.·Rawson, S.·Scavenius, C.·Enghild, J.·Bereta, G.·Pothula, K.·Kleinekathoefer, U.·Basle, A.·Ranson, N.·Potempa, J.·van den Berg, B.

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Abstract

Porphyromonas gingivalis, an asaccharolytic Bacteroidetes, is a keystone pathogen in human periodontitis that may also contribute to the development of other chronic inflammatory diseases, such as rheumatoid arthritis, cardiovascular disease and Alzheimers disease. P. gingivalis utilizes protease-generated peptides derived from extracellular proteins for growth, but how those peptides enter the cell is not clear. Here we identify RagAB as the outer membrane importer for 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 TonB-dependent transporter RagA. Cryo-electron microscopy structures reveal the opening of the RagB lid and thus provide direct evidence for a \"pedal bin\" nutrient uptake mechanism. Together with mutagenesis, peptide binding studies and RagAB peptidomics, our work identifies RagAB as a dynamic OM oligopeptide acquisition machine with considerable substrate selectivity that is essential for the efficient utilisation of proteinaceous nutrients by P. gingivalis.

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Madej, M., White, J., Nowakowska, Z., Rawson, S., Scavenius, C., Enghild, J., Bereta, G., Pothula, K., Kleinekathoefer, U., Basle, A., Ranson, N., Potempa, J., van den Berg, B.. 2019-09-04. Dynamic oligopeptide acquisition by the RagAB transporter from Porphyromonas gingivalis. https://doi.org/10.1101/755678

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