Nature (London), 2020-04, Vol.580 (7803), p.413-417
2020
Details
- Autor(en) / Beteiligte
- Titel
- The ABC exporter IrtAB imports and reduces mycobacterial siderophores
- Ist Teil von
- Nature (London), 2020-04, Vol.580 (7803), p.413-417
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Intracellular replication of the deadly pathogen Mycobacterium tuberculosis relies on the production of small organic molecules called siderophores that scavenge iron from host proteins . M. tuberculosis produces two classes of siderophore, lipid-bound mycobactin and water-soluble carboxymycobactin . Functional studies have revealed that iron-loaded carboxymycobactin is imported into the cytoplasm by the ATP binding cassette (ABC) transporter IrtAB , which features an additional cytoplasmic siderophore interaction domain . However, the predicted ABC exporter fold of IrtAB is seemingly contradictory to its import function. Here we show that membrane-reconstituted IrtAB is sufficient to import mycobactins, which are then reduced by the siderophore interaction domain to facilitate iron release. Structure determination by X-ray crystallography and cryo-electron microscopy not only confirms that IrtAB has an ABC exporter fold, but also reveals structural peculiarities at the transmembrane region of IrtAB that result in a partially collapsed inward-facing substrate-binding cavity. The siderophore interaction domain is positioned in close proximity to the inner membrane leaflet, enabling the reduction of membrane-inserted mycobactin. Enzymatic ATPase activity and in vivo growth assays show that IrtAB has a preference for mycobactin over carboxymycobactin as its substrate. Our study provides insights into an unusual ABC exporter that evolved as highly specialized siderophore-import machinery in mycobacteria.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0028-0836eISSN: 1476-4687DOI: 10.1038/s41586-020-2136-9Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7170716
- Format
- –
- Schlagworte
- ABC transporters, Adenosine triphosphatase, Analysis, ATP synthesis, ATP-Binding Cassette Transporters - chemistry, ATP-Binding Cassette Transporters - genetics, ATP-Binding Cassette Transporters - metabolism, Bacterial Proteins - chemistry, Bacterial Proteins - genetics, Bacterial Proteins - metabolism, Binding, Binding sites, Chromatography, Control, Cryoelectron Microscopy, Crystallography, Crystallography, X-Ray, Cytoplasm, Domains, Electron microscopy, Experiments, Exports, Imports, Influence, Iron, Lipids, Membranes, Microscopy, Models, Molecular, Mycobacterium smegmatis - chemistry, Mycobacterium smegmatis - genetics, Mycobacterium smegmatis - metabolism, Mycobacterium tuberculosis, Organic chemistry, Protein Structure, Quaternary, Protein Structure, Tertiary, Proteins, Siderophores, Siderophores (Microbiology), Siderophores - metabolism, Structure, Substrates, Tuberculosis, X-ray crystallography