Structural insights into substrate recognition by the type Ⅶ secretion system
作者机构：Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and TechnologyShanghaiTech UniversityShanghai 201210China CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China State Key Laboratory of Medicinal Chemical BiologyCollege of Life Sciences and College of PharmacyNankai UniversityTianjin 300353China Laboratory of Structural BiologyTsinghua UniversityBeijing 100084China National Laboratory of BiomacromoleculesCAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China School of Chemistry and Molecular BiosciencesThe University of QueenslandBrisbaneQLD 4072Australia University of Chinese Academy of SciencesBeijing 100101China
出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)
年 卷 期：2020年第11卷第2期
页 面：124-137页
核心收录：
学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100103[医学-病原生物学] 0703[理学-化学] 0836[工学-生物工程] 10[医学]
基 金：We are extremely grateful to the National Centre for Protein Science Shanghai(Protein Expression and Purification System)for their instrumental support and technical assistance.We thank the staff from beamlines BL18U and BL19U1 at Shanghai Synchrotron Radiation Facility(Shanghai,China)and beamline BL41XU at SPring-8(Hyogo,Japan)for assistance during data collection.We also thank Prof.Rongguang Zhang and Dr.Jinwei Zhu for providing laboratory resources.This work was supported by Grants from the National Key Research and Development Program of China(Grant No.2017YFC0840300) the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB08020200) the National Natural Science Foundation of China(Grant Nos.81520108019,31500607).
主 题：type VII secretion system Mycobacterium tuberculosis ATPase virulence factor substrate recognition
摘 要：Type VII secretion systems(T7SSs)are found in many disease related bacteria including Mycobacterium tuberculosis(Mtb).ESX-1[early secreted antigen 6 kilodaltons(ESAT-6)system 1]is one of the five subtypes(ESX-1?5)of T7SSs in Mfb,where it delivers virulence factors into host macrophages during infection.However,little is known about the molecular details as to how this occurs.Here,we provide high-resolution crystal structures of the C-terminal ATPase3 domains of EccC subunits from four different Mtb T7SS subtypes.These structures adopt a classic RecA-like a/p fold with a conserved Mg-ATP binding site.The structure of EccCbl in complex with the C-terminal peptide of EsxB identifies the location of substrate recognition site and shows how the specific signaling module XxxxMxFfor Mtb ESX-1 binds to this site resulting in a translation of the bulge loop.A comparison of all the ATPase3 structures shows there are significant differences in the shape and composition of the signal recognition pockets across the family,suggesting that distinct signaling sequences of substrates are required to be specifically recognized by different T7SSs.A hexameric model of the EccC-ATPase3 is proposed and shows the recognition pocket is located near the central substrate translocation channel.The diameter of the channel is?25-A,with a size that would allow helix-bundle shaped substrate proteins to bind and pass through.Thus,our work provides new molecular insights into substrate recognition for Mtb T7SS subtypes and also a possible transportation mechanism for substrate and/or virulence factor secretion.
维普期刊数据库