Crystal structures of the outer membrane transporter FoxA provide novel insights into TonB-mediated siderophore uptake and signalling
- Resource Type
- Authors
- Henning Tidow; Inokentijs Josts; Katharina Veith
- Source
- Subject
- Siderophore
Ferrioxamine B
biology
Chemistry
Transporter
Crystal structure
biochemical phenomena, metabolism, and nutrition
biology.organism_classification
Cell biology
Signalling
polycyclic compounds
bacteria
Secretion
Bacterial outer membrane
Bacteria
- Language
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 fromPseudomonas 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.