Cryo-EM structures for the Mycobacterium tuberculosis iron-loaded siderophore transporter IrtAB.

Shan Sun; Yan Gao; Xiaolin Yang; Xiuna Yang; Tianyu HU; Jingxi Liang; Zhiqi Xiong; Yuting Ran; Pengxuan Ren; Fang Bai; Luke W Guddat; Haitao Yang; Zihe Rao; Bing Zhang

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Cryo-EM structures for the Mycobacterium tuberculosis iron-loaded siderophore transporter IrtAB.

Author: Shan SUN ¹ ; Yan GAO ¹ ; Xiaolin YANG ¹ ; Xiuna YANG ¹ ; Tianyu HU ¹ ; Jingxi LIANG ² ; Zhiqi XIONG ³ ; Yuting RAN ¹ ; Pengxuan REN ¹ ; Fang BAI ¹ ; Luke W GUDDAT ⁴ ; Haitao YANG ¹ ; Zihe RAO ¹ ; Bing ZHANG ¹
Author Information

1. Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
2. State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300353, China.
3. Laboratory of Structural Biology, Tsinghua University, Beijing 100084, China.
4. School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia.
Publication Type:Research Support, Non-U.S. Gov't
Keywords: Mycobacterium tuberculosis; ABC exporter-like importer; ABC transporter; IrtAB; iron-loaded siderophore
MeSH: Siderophores/metabolism*; Iron/metabolism*; Mycobacterium tuberculosis/metabolism*; Cryoelectron Microscopy; Adenosine Triphosphate/metabolism*; ATP-Binding Cassette Transporters
From: Protein & Cell 2023;14(6):448-458
CountryChina
Language:English
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.