Structural insights into a novel family of integral membrane siderophore reductases

Proc Natl Acad Sci U S A. 2021 Aug 24;118(34):e2101952118. doi: 10.1073/pnas.2101952118.

Abstract

Gram-negative bacteria take up the essential ion Fe3+ as ferric-siderophore complexes through their outer membrane using TonB-dependent transporters. However, the subsequent route through the inner membrane differs across many bacterial species and siderophore chemistries and is not understood in detail. Here, we report the crystal structure of the inner membrane protein FoxB (from Pseudomonas aeruginosa) that is involved in Fe-siderophore uptake. The structure revealed a fold with two tightly bound heme molecules. In combination with in vitro reduction assays and in vivo iron uptake studies, these results establish FoxB as an inner membrane reductase involved in the release of iron from ferrioxamine during Fe-siderophore uptake.

Keywords: crystal structure; heme; integral membrane protein; reductase; siderophore uptake.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Biological Transport
  • Iron / metabolism*
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism
  • Oxidoreductases / chemistry*
  • Oxidoreductases / metabolism
  • Protein Conformation
  • Pseudomonas aeruginosa / growth & development
  • Pseudomonas aeruginosa / metabolism*
  • Siderophores / metabolism*

Substances

  • Bacterial Proteins
  • Membrane Proteins
  • Siderophores
  • Iron
  • Oxidoreductases