7WIX

Cryo-EM structure of Mycobacterium tuberculosis irtAB in complex with ADP

Summary for 7WIX

• Entry DOI: 10.2210/pdb7wix/pdb
• EMDB information: 32539
• Descriptor: Mycobactin import ATP-binding/permease protein IrtA, Mycobactin import ATP-binding/permease protein IrtB, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: irtab, abc exporter-liker importer, iron-loaded siderophore, mycobacterium tuberculosis, membrane protein
• Biological source: Mycobacterium tuberculosis H37Rv; More
• Total number of polymer chains: 2
• Total formula weight: 154959.49

Authors

Zhang, B.,Sun, S.,Yang, H.,Rao, Z. (deposition date: 2022-01-05, release date: 2023-01-25, Last modification date: 2024-04-10)

Primary citation

Sun, S.,Gao, Y.,Yang, X.,Yang, X.,Hu, T.,Liang, J.,Xiong, Z.,Ran, Y.,Ren, P.,Bai, F.,Guddat, L.W.,Yang, H.,Rao, Z.,Zhang, B.
Cryo-EM structures for the Mycobacterium tuberculosis iron-loaded siderophore transporter IrtAB.
Protein Cell, 14:448-458, 2023

PubMed Abstract: The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts the canonical type IV exporter fold. Herein, we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP, ADP, or ATP analogue (AMP-PNP) at resolutions ranging from 2.8 to 3.5 Å. The structure of IrtAB bound ATP-Mg2+ shows a "head-to-tail" dimer of nucleotide-binding domains (NBDs), a closed amphipathic cavity within the transmembrane domains (TMDs), and a metal ion liganded to three histidine residues of IrtA in the cavity. Cryo-electron microscopy (Cryo-EM) structures and ATP hydrolysis assays show that the NBD of IrtA has a higher affinity for nucleotides and increased ATPase activity compared with IrtB. Moreover, the metal ion located in the TM region of IrtA is critical for the stabilization of the conformation of IrtAB during the transport cycle. This study provides a structural basis to explain the ATP-driven conformational changes that occur in IrtAB.

PubMed: 36882106
DOI: 10.1093/procel/pwac060

Experimental method

ELECTRON MICROSCOPY (3.53 Å)