The Accessory SecA2 System of Mycobacteria Requires ATP Binding and the Canonical SecA1.
The Accessory SecA2 System of Mycobacteria Requires ATP Binding and the Canonical SecA1.
复制标题
分枝杆菌的辅助 SecA2 系统需要 ATP 结合和规范 SecA1。
DOI：
10.1074/jbc.m900325200
复制
发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Braunstein,Miriam
中科院分区：
文献类型：
--
作者：
Rigel,NathanW;Gibbons,HenryS;McCann,JessicaR;McDonough,JustinA;Kurtz,Sherry;Braunstein,Miriam
在细菌中，大多数输出的蛋白质通过一般的Sec途径从它们在细胞质中的合成位点穿过细胞质膜转运。必需的SecA ATP酶为这种Sec介导的输出提供动力。分枝杆菌具有两个非冗余SecA同源物：SecA1和SecA2。在致病性结核分枝杆菌（Mycobacteriumtuberculosis）和非致病性模式结核分枝杆菌（Mycobacteriumsmegalovirus）中，SecA1是蛋白质输出所必需的，是SecA的“管家”，而SecA2是输出特定蛋白质子集的辅助SecA。InM.辅助SecA2通路在结核病毒力中起作用。在这项研究中，我们发现了分枝杆菌SecA2蛋白的基本特性及其输出选择蛋白的途径。通过构建编码ATP结合缺陷蛋白的secA2突变等位基因，我们发现ATP结合是SecA2功能所必需的。SecA2突变体蛋白不能结合ATP的非功能性和显性负。通过评估每个SecA的亚细胞分布，SecA1被证明是平均分配之间的胞质和细胞包膜部分，而SecA2主要定位于胞质。最后，我们发现，典型的SecA1在SecA2依赖的出口过程中发挥作用。SecA2辅助输出系统对分枝杆菌的生理和毒力具有重要作用。这些研究有助于建立这种新型专门蛋白质输出途径的机制。
In bacteria, the majority of exported proteins are transported by the general Sec pathway from their site of synthesis in the cytoplasm across the cytoplasmic membrane. The essential SecA ATPase powers this Sec-mediated export. Mycobacteria possess two nonredundant SecA homologs: SecA1 and SecA2. In pathogenicMycobacterium tuberculosisand the nonpathogenic model mycobacteriumMycobacterium smegmatis, SecA1 is essential for protein export and is the “housekeeping” SecA, whereas SecA2 is an accessory SecA that exports a specific subset of proteins. InM. tuberculosisthe accessory SecA2 pathway plays a role in virulence. In this study, we uncovered basic properties of the mycobacterial SecA2 protein and its pathway for exporting select proteins. By constructingsecA2mutant alleles that encode proteins defective in ATP binding, we showed that ATP binding is required for SecA2 function. SecA2 mutant proteins unable to bind ATP were nonfunctional and dominant negative. By evaluating the subcellular distribution of each SecA, SecA1 was shown to be equally divided between cytosolic and cell envelope fractions, whereas SecA2 was predominantly localized to the cytosol. Finally, we showed that the canonical SecA1 has a role in the process of SecA2-dependent export. The accessory SecA2 export system is important to the physiology and virulence of mycobacteria. These studies help establish the mechanism of this new type of specialized protein export pathway.