Identification and architecture of a putative secretion tube across mycobacterial outer envelope.

Identification and architecture of a putative secretion tube across mycobacterial outer envelope.
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跨分枝杆菌外膜的假定分泌管的识别和结构

DOI:
10.1126/sciadv.abg5656
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发表时间:
2021-08
期刊:
影响因子:
13.6
通讯作者:
Gong W
Gong W
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Cai X;Liu L;Qiu C;Wen C;He Y;Cui Y;Li S;Zhang X;Zhang L;Tian C;Bi L;Zhou ZH;Gong W

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结构和体内功能分析揭示了分枝杆菌外膜上可能存在蛋白质分泌管。引起结核病的分枝杆菌具有由复杂结构形成的厚细胞壁和荚膜层。跨越这些屏障的蛋白质分泌取决于专门的蛋白质分泌系统,但尚未有报道。我们发现结核分枝杆菌 Rv3705c 及其在耻垢分枝杆菌中的同源 MSMEG_6251 是分枝杆菌包膜 (TiME) 中的管形成蛋白。这两种蛋白质的晶体学和冷冻电镜结构表明,两种蛋白质均形成旋转对称环。两层 TiME 环以尾对尾的方式堆积在一起形成环形复合体,然后再堆叠在一起形成管。耻垢分枝杆菌 TiME 主要在细胞壁和荚膜中检测到。敲除TiME基因显着降低了耻垢分枝杆菌培养基中分泌蛋白的量,并且该基因在敲除菌株中的表达部分恢复了分泌蛋白的水平。因此,我们的结构和功能数据表明,TiME 形成穿过分枝杆菌外膜的蛋白质运输管。
Structural and in vivo functional analyses reveal a possible protein secretion tube across the mycobacterial outer envelope. Tuberculosis-causing mycobacteria have thick cell-wall and capsule layers that are formed from complex structures. Protein secretion across these barriers depends on a specialized protein secretion system, but none has been reported. We show that Mycobacterium tuberculosis Rv3705c and its homologous MSMEG_6251 in Mycobacterium smegmatis are tube-forming proteins in the mycobacterial envelope (TiME). Crystallographic and cryo-EM structures of these two proteins show that both proteins form rotationally symmetric rings. Two layers of TiME rings pack together in a tail-to-tail manner into a ring-shaped complex, which, in turn, stacks together to form tubes. M. smegmatis TiME was detected mainly in the cell wall and capsule. Knocking out the TiME gene markedly decreased the amount of secreted protein in the M. smegmatis culture medium, and expression of this gene in knocked-out strain partially restored the level of secreted protein. Our structure and functional data thus suggest that TiME forms a protein transport tube across the mycobacterial outer envelope.
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