9G2S

Cryo-EM structure of IrtAB 2xEQ, Q249R_IrtB mutant in LMNG

Summary for 9G2S

• Entry DOI: 10.2210/pdb9g2s/pdb
• Related: 6TEJ 9FW3 9FXC 9G2K 9G2L 9G2M 9G2P 9G2T 9G2V 9G2X 9G2Y 9G2Z 9G36 9G37 9GL3
• EMDB information: 10319 50982
• Descriptor: Mycobactin import ATP-binding/permease protein IrtA, Mycobactin import ATP-binding/permease protein IrtB, ADENOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: abc transporter, type iv abc importer siderophore, mycobactin, heterodimeric abc transporter, membrane protein
• Biological source: Mycolicibacterium thermoresistibile ATCC 19527; More
• Total number of polymer chains: 2
• Total formula weight: 127024.93

Authors

Gonda, I.,Seeger, M.A. (deposition date: 2024-07-11, release date: 2024-12-18, Last modification date: 2025-02-12)

Primary citation

Gonda, I.,Sorrentino, S.,Galazzo, L.,Lichti, N.P.,Arnold, F.M.,Mehdipour, A.R.,Bordignon, E.,Seeger, M.A.
The mycobacterial ABC transporter IrtAB employs a membrane-facing crevice for siderophore-mediated iron uptake.
Nat Commun, 16:1133-1133, 2025

PubMed Abstract: The mycobacterial ABC transporter IrtAB features an ABC exporter fold, yet it imports iron-charged siderophores called mycobactins. Here, we present extensive cryo-EM analyses and DEER measurements, revealing that IrtAB alternates between an inward-facing and an outward-occluded conformation, but does not sample an outward-facing conformation. When IrtAB is locked in its outward-occluded conformation in nanodiscs, mycobactin is bound in the middle of the lipid bilayer at a membrane-facing crevice opening at the heterodimeric interface. Mutations introduced at the crevice abrogate mycobactin import and in corresponding structures, the crevice is collapsed. A conserved triple histidine motif coordinating a zinc ion is present below the mycobactin binding site. Substitution of these histidine residues with alanine results in a decoupled transporter, which hydrolyzes ATP, but lost its capacity to import mycobactins. Our data suggest that IrtAB imports mycobactin via a credit-card mechanism in a transport cycle that is coupled to the presence of zinc.

PubMed: 39880813
DOI: 10.1038/s41467-024-55136-7

Experimental method

ELECTRON MICROSCOPY (2.9 Å)