C末端信号序列促进结核分枝杆菌毒力因子的分泌。

C-terminal signal sequence promotes virulence factor secretion in Mycobacterium tuberculosis.

作者信息

Champion Patricia A Digiuseppe, Stanley Sarah A, Champion Matthew M, Brown Eric J, Cox Jeffery S

机构信息

Department of Microbiology and Immunology, University of California, San Francisco, 600 16th Street, Campus Box 2200, San Francisco, CA 94143-2200, USA.

出版信息

Science. 2006 Sep 15;313(5793):1632-6. doi: 10.1126/science.1131167.

DOI:10.1126/science.1131167

PMID:16973880

Abstract

Mycobacterium tuberculosis uses the ESX-1/Snm system [early secreted antigen 6 kilodaltons (ESAT-6) system 1/secretion in mycobacteria] to deliver virulence factors into host macrophages during infection. Despite its essential role in virulence, the mechanism of ESX-1 secretion is unclear. We found that the unstructured C terminus of the CFP-10 substrate was recognized by Rv3871, a cytosolic component of the ESX-1 system that itself interacts with the membrane protein Rv3870. Point mutations in the signal that abolished binding of CFP-10 to Rv3871 prevented secretion of the CFP-10 (culture filtrate protein, 10 kilodaltons)/ESAT-6 virulence factor complex. Attachment of the signal to yeast ubiquitin was sufficient for secretion from M. tuberculosis cells, demonstrating that this ESX-1 signal is portable.

摘要

结核分枝杆菌利用ESX-1/Snm系统[早期分泌抗原6千道尔顿（ESAT-6）系统1/分枝杆菌中的分泌]在感染期间将毒力因子递送至宿主巨噬细胞。尽管其在毒力中起关键作用，但ESX-1分泌的机制尚不清楚。我们发现CFP-10底物的无结构C末端被Rv3871识别，Rv3871是ESX-1系统的胞质成分，其自身与膜蛋白Rv3870相互作用。消除CFP-10与Rv3871结合的信号中的点突变阻止了CFP-10（培养滤液蛋白，10千道尔顿）/ESAT-6毒力因子复合物的分泌。该信号与酵母泛素的连接足以从结核分枝杆菌细胞中分泌，表明该ESX-1信号是可转移的。