9FXC

Cryo-EM structure of IrtAB in inward-facing state in nanodisc

9FXC の概要

• エントリーDOI: 10.2210/pdb9fxc/pdb
• 関連するPDBエントリー: 6TEJ
• EMDBエントリー: 10319 50848
• 分子名称: Mycobactin import ATP-binding/permease protein IrtA, Mycobactin import ATP-binding/permease protein IrtB, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER (3 entities in total)
• 機能のキーワード: abc transporter, type iv abc importer siderophore, mycobactin, heterodimeric abc transporter, membrane protein
• 由来する生物種: Mycolicibacterium thermoresistibile ATCC 19527; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 160102.57

構造登録者

Gonda, I.,Seeger, M.A. (登録日: 2024-07-01, 公開日: 2024-12-18, 最終更新日: 2025-02-12)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.6 Å)