Structural insights into substrate recognition by the type VII secretion system
2019-11-23
发表期刊PROTEIN & CELL (IF:13.6[JCR-2023],17.7[5-Year])
ISSN1674-800X
EISSN1674-8018
发表状态已发表
DOI10.1007/s13238-019-00671-z
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-15) of T7SSs in Mtb, 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 ATPase(3) domains of EccC subunits from four different Mtb T7SS subtypes. These structures adopt a classic RecA-like /beta fold with a conserved Mg-ATP binding site. The structure of EccCb1 in complex with the C-terminal peptide of EsxB identifies the location of substrate recognition site and shows how the specific signaling module "LxxxMxF" for Mtb ESX-1 binds to this site resulting in a translation of the bulge loop. A comparison of all the ATPase(3) 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-ATPase(3) is proposed and shows the recognition pocket is located near the central substrate translocation channel. The diameter of the channel is 25-angstrom, 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.

关键词type VII secretion system Mycobacterium tuberculosis ATPase virulence factor substrate recognition
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收录类别SCI ; SCIE ; CSCD
语种英语
资助项目National Natural Science Foundation of China[81520108019] ; National Natural Science Foundation of China[31500607]
WOS研究方向Cell Biology
WOS类目Cell Biology
WOS记录号WOS:000498011400001
CSCD记录号CSCD:6699204
出版者SPRINGEROPEN
WOS关键词MYCOBACTERIUM-BOVIS BCG ; VIRULENCE FACTORS ; TUBERCULOSIS ; ESAT-6 ; PROTEINS ; GRANULOMA ; SEQUENCE ; COMPLEX ; RD1 ; TRANSLOCATION
原始文献类型Article
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/104321
专题生命科学与技术学院_博士生
免疫化学研究所_特聘教授组_饶子和组
生命科学与技术学院_硕士生
免疫化学研究所_PI研究组_杨海涛组
免疫化学研究所_PI研究组_李俊组
通讯作者Li, Jun; Rao, Zihe
作者单位
1.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China
2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, Shanghai 200031, Peoples R China
4.Nankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Tianjin 300353, Peoples R China
5.Nankai Univ, Coll Pharm, Tianjin 300353, Peoples R China
6.Tsinghua Univ, Lab Struct Biol, Beijing 100084, Peoples R China
7.Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing 100101, Peoples R China
8.Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Qld 4072, Australia
9.Univ Chinese Acad Sci, Beijing 100101, Peoples R China
第一作者单位免疫化学研究所;  生命科学与技术学院
通讯作者单位免疫化学研究所;  生命科学与技术学院
第一作者的第一单位免疫化学研究所
推荐引用方式
GB/T 7714
Wang, Shuhui,Zhou, Kaixuan,Yang, Xiaolin,et al. Structural insights into substrate recognition by the type VII secretion system[J]. PROTEIN & CELL,2019.
APA Wang, Shuhui.,Zhou, Kaixuan.,Yang, Xiaolin.,Zhang, Bing.,Zhao, Yao.,...&Rao, Zihe.(2019).Structural insights into substrate recognition by the type VII secretion system.PROTEIN & CELL.
MLA Wang, Shuhui,et al."Structural insights into substrate recognition by the type VII secretion system".PROTEIN & CELL (2019).
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