Cryo-EM reveals unique structural features of the FhuCDB Escherichia coli ferrichrome importer

• Published in: Communications biology Vol. 4; no. 1; p. 1383
• Main Authors: Hu, Wenxin, Zheng, Hongjin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09-12-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 101/28; 631/45/535/1258/1259; 631/45/612/1237; 82; Adenosine triphosphatase; Biological Transport; Biology; Biomedical and Life Sciences; Cryoelectron Microscopy; E coli; Electron microscopy; Escherichia coli; Escherichia coli - genetics; Escherichia coli - ultrastructure; Ferrichrome - metabolism; Iron; Life Sciences; Mutagenesis; Siderophores; Siderophores - metabolism
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-021-02916-2

As one of the most elegant biological processes developed in bacteria, the siderophore-mediated iron uptake demands the action of specific ATP-binding cassette (ABC) importers. Although extensive studies have been done on various ABC importers, the molecular basis of these iron-chelated-siderophore importers are still not fully understood. Here, we report the structure of a ferrichrome importer FhuCDB from
Escherichia coli
at 3.4 Å resolution determined by cryo electron microscopy. The structure revealed a monomeric membrane subunit of FhuB with a substrate translocation pathway in the middle. In the pathway, there were unique arrangements of residues, especially layers of methionines. Important residues found in the structure were interrogated by mutagenesis and functional studies. Surprisingly, the importer’s ATPase activity was decreased upon FhuD binding, which deviated from the current understanding about bacterial ABC importers. In summary, to the best of our knowledge, these studies not only reveal a new structural twist in the type II ABC importer subfamily, but also provide biological insights in the transport of iron-chelated siderophores.
Wenxin Hu et al. use cryo-EM and biochemical assays to describe the functional activity and structure of the ferrichrome importer, FhuCDB in
E. coli
. Their results provide further insight on the mechanism of siderophore transport in bacteria.