Ternary structure of the outer membrane transporter FoxA provides insights into TonB-mediated siderophore uptake

  1. Inokentijs Josts
  2. Katharina Veith
  3. Henning Tidow  Is a corresponding author
  1. University of Hamburg, Germany

Abstract

Many microbes and fungi acquire the essential ion Fe3+ through the synthesis and secretion of high-affinity chelators termed siderophores. In Gram-negative bacteria, these ferric-siderophore complexes are actively taken up using highly specific TonB-dependent transporters (TBDTs) located in the outer bacterial membrane (OM). However, the detailed mechanism of how the inner-membrane protein TonB connects to the transporters in the OM as well as the interplay between siderophore- and TonB-binding to the transporter is still poorly understood. Here, we present three crystal structures of the TBDT FoxA from Pseudomonas aeruginosa (containing a signalling domain) in complex with the siderophore ferrioxamine B and TonB and combine them with a detailed analysis of binding constants. The structures show that both siderophore and TonB-binding is required to form a translocation-competent state of the FoxA transporter in a two-step TonB-binding mechanism. The complex structure also indicates how TonB-binding influences the orientation of the signalling domain.

Data availability

Structural coordinates and structure factors have been deposited in the RCSB Protein Data Bank under accession numbers 6I96, 6I97, and 6I98 (see Table 1, Suppl. Info.).

The following data sets were generated

Article and author information

Author details

  1. Inokentijs Josts

    Department of Chemistry, University of Hamburg, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Katharina Veith

    Department of Chemistry, University of Hamburg, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Henning Tidow

    Department of Chemistry, University of Hamburg, Hamburg, Germany
    For correspondence
    tidow@chemie.uni-hamburg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4702-9332

Funding

Deutsche Forschungsgemeinschaft (DFG EXC 1074)

  • Henning Tidow

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Volker Dötsch, Goethe University, Germany

Publication history

  1. Received: May 16, 2019
  2. Accepted: August 5, 2019
  3. Accepted Manuscript published: August 6, 2019 (version 1)
  4. Version of Record published: August 19, 2019 (version 2)

Copyright

© 2019, Josts et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Inokentijs Josts
  2. Katharina Veith
  3. Henning Tidow
(2019)
Ternary structure of the outer membrane transporter FoxA provides insights into TonB-mediated siderophore uptake
eLife 8:e48528.
https://doi.org/10.7554/eLife.48528

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