Core component EccB1 of the Mycobacterium tuberculosis type VII secretion system is a periplasmic ATPase
Core component EccB1 of the Mycobacterium tuberculosis type VII secretion system is a periplasmic ATPase
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DOI：
10.1096/fj.15-270843
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发表时间：
2015-12
期刊：
影响因子：
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通讯作者：
Xiao‐Li Zhang;De-Feng Li;Joy Fleming;Liwei Wang;Ying Zhou;Dacheng Wang;Xian-En Zhang;L. Bi
中科院分区：
文献类型：
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作者：
Xiao‐Li Zhang;De-Feng Li;Joy Fleming;Liwei Wang;Ying Zhou;Dacheng Wang;Xian-En Zhang;L. Bi
致病性分枝杆菌通过VII型分泌系统（T7 SS）/早期分泌的抗原靶点-6 kDa分泌系统（ESX）将毒力因子转运穿过其复杂的细胞壁。ESX保守组分（Ecc）B是T7 SS结构的核心组分，被预测为膜结合蛋白，但对其结构和功能知之甚少。在这里，我们的特点EccB 1，表明它是一个ATP酶没有序列或结构同源性，位于结核分枝杆菌H37 Rv的细胞包膜中的其他ATP酶。我们获得了EccB 1-ΔN72截短跨膜螺旋的晶体结构，并进行了建模和ATP对接研究，表明EccB 1可能以六聚体形式存在。EccB 1同源物的序列比对和ATP酶活性测定表明，在EccB 1-ΔN72的N-和C-末端存在3个保守基序，它们在EccB 1-Δ N72单体的2个膜近端结构域之间组装在一起。EccB 1六聚体的模型显示，2个保守基序参与ATP酶活性，并形成位于2个相邻分子表面的ATP结合口袋。我们的研究结果表明，EccB可能在T7 SS毒力因子的运输中充当能量提供者，并可能参与穿过菌膜的通道的形成。张X-L李D-F Fleming，J.，Wang，L. -W.，Zhou，Y.，（1996年），中国科学院，王华盛顿张X-E毕，L-J结核分枝杆菌VII型分泌系统的核心组分EccB 1是周质ATP酶。FASEB J.29，4804-4814（2015）. www.fasebj.org
Pathogenic mycobacteria transport virulence factors across their complex cell wall via a type VII secretion system (T7SS)/early secreted antigenic target‐6 of kDa secretion system (ESX). ESX conserved component (Ecc) B, a core component of the T7SS architecture, is predicted to be a membrane bound protein, but little is known about its structure and function. Here, we characterize EccB1, showing that it is an ATPase with no sequence or structural homology to other ATPases located in the cell envelope of Mycobacterium tuberculosis H37Rv. We obtained the crystal structure of an EccB1‐ΔN72 truncated transmembrane helix and performed modeling and ATP docking studies, showing that EccB1 likely exists as a hexamer. Sequence alignment and ATPase activity determination of EccB1 homologues indicated the presence of 3 conserved motifs in the N‐ and C‐terminals of EccB1‐ΔN72 that assemble together between 2 membrane proximal domains of the EccB1‐ΔN72 monomer. Models of the EccB1 hexamer show that 2 of the conserved motifs are involved in ATPase activity and form an ATP binding pocket located on the surface of 2 adjacent molecules. Our results suggest that EccB may act as the energy provider in the transport of T7SS virulence factors and may be involved in the formation of a channel across the mycomembrane.—Zhang, X.‐L., Li, D.‐F., Fleming, J., Wang, L.‐W., Zhou, Y., Wang, D.‐C., Zhang, X.‐E., Bi, L.‐J. Core component EccB1 of the Mycobacterium tuberculosis type VII secretion system is a periplasmic ATPase. FASEB J. 29, 4804–4814 (2015). www.fasebj.org