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

Lookup NU author(s): Mariusz Madej, Dr Arnaud Basle, Professor Bert van den Berg

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by Nature Publishing Group, 2020.

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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 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 RagA TonB-dependent transporter. 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, selective OM oligopeptide acquisition machine that is essential for the efficient utilisation of proteinaceous nutrients by P. gingivalis.


Publication metadata

Author(s): Madej M, White JBR, Nowakowska Z, Rawson S, Scavenius C, Enghild JJ, Bereta GP, Pothula K, Kleinekathoefer U, Baslé A, Ranson NA, Potempa J, van den Berg B

Publication type: Article

Publication status: Published

Journal: Nature Microbiology

Year: 2020

Volume: 5

Pages: 1016-1025

Print publication date: 01/08/2020

Online publication date: 11/05/2020

Acceptance date: 31/03/2020

Date deposited: 13/06/2020

ISSN (electronic): 2058-5276

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/s41564-020-0716-y

DOI: 10.1038/s41564-020-0716-y

PubMed id: 32393857


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