9GI0

Truncated MmpL4 in detergent

Summary for 9GI0

• Entry DOI: 10.2210/pdb9gi0/pdb
• EMDB information: 51366
• Descriptor: Acyl carrier protein, Siderophore exporter MmpL4, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (3 entities in total)
• Functional Keywords: rnd superfamily mmpl family siderophore export drug resistance acyl carrier protein, membrane protein
• Biological source: Mycobacterium tuberculosis; More
• Total number of polymer chains: 2
• Total formula weight: 93198.00

Authors

Earp, J.C.,Garaeva, A.A.,Seeger, M.A. (deposition date: 2024-08-16, release date: 2025-02-19, Last modification date: 2025-03-05)

Primary citation

Earp, J.C.,Garaeva, A.A.,Meikle, V.,Niederweis, M.,Seeger, M.A.
Structural basis of siderophore export and drug efflux by Mycobacterium tuberculosis.
Nat Commun, 16:1934-1934, 2025

PubMed Abstract: To replicate and cause disease, Mycobacterium tuberculosis secretes siderophores called mycobactins to scavenge iron from the human host. Two closely related transporters, MmpL4 and MmpL5, are required for mycobactin secretion and drug efflux. In clinical strains, overproduction of MmpL5 confers resistance towards bedaquiline and clofazimine, key drugs to combat multidrug resistant tuberculosis. Here, we present cryogenic-electron microscopy structures of MmpL4 and identify a mycobactin binding site, which is accessible from the cytosol and also required for bedaquiline efflux. An unusual coiled-coil domain predicted to extend 130 Å into the periplasm is essential for mycobactin and bedaquiline efflux by MmpL4 and MmpL5. The mycobacterial acyl carrier protein MbtL forms a complex with MmpL4, indicating that mycobactin synthesis and export are coupled. Thus, MmpL4 and MmpL5 constitute the core components of a unique multi-subunit machinery required for iron acquisition and drug efflux by M. tuberculosis.

PubMed: 39994240
DOI: 10.1038/s41467-025-56888-6

Experimental method

ELECTRON MICROSCOPY (3 Å)