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

作　　者：Shan Sun Yan Gao Xiaolin Yang Xiuna Yang Tianyu Hu Jingxi Liang Zhiqi Xiong Yuting Ran Pengxuan Ren Fang Bai Luke WGuddat Haitao Yang Zihe Rao Bing Zhang 

机构地区：[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]National Laboratory of Biomacromolecules,CAS Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China [5]School of Chemistry and Molecular Biosciences,The University of Queensland,Brisbane,Queensland 4072,Australia [6]CAS Center for Excellence in Molecular Cell Science,Shanghai Institute of Biochemistry and Cell Biology,Chinese Academy of Sciences,Shanghai 200031,China [7]University of Chinese Academy of Sciences,Beijing 100101,China [8]Shanghai Clinical Research and Trial Center,Shanghai 201210,China

出　　处：《Protein & Cell》2023年第6期448-458,共11页蛋白质与细胞（英文版）

基　　金：supported by grants from the National Key Research and Development Program of China(Grant No.2022YFC2302900);the National Natural Science Foundation of China(Grant No.32171217 to B.Z.);Shanghai Sailing Program(Grant No.21YF1429700 to B.Z.);Young Elite Scientists Sponsorship Program by CAST(Grant No.2021QNRC001);the Lingang Laboratory(Grant No.LG202101-01-08);Shanghai Municipal Science and Technology Major Project(Grant No.ZD2021CY001);Science and Technology Commission of Shanghai Municipality(Grant No.20XD1422900 to H.Y.);the Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine,Shanghaitech University.

摘　　要：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 3.5Å.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.

关 键 词：ABC exporter-like importer iron-loaded siderophore IrtAB Mycobacterium tuberculosis ABC transporter 

分 类 号：R52[医药卫生—内科学]