Secretion signal recognition by YscN, the Yersinia type III secretion ATPase
Secretion signal recognition by YscN, the Yersinia type III secretion ATPase
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DOI：
10.1073/pnas.0605974103
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发表时间：
2006-10-31
影响因子：
11.1
通讯作者：
Schneewind, Olaf
中科院分区：
文献类型：
--
作者：
Sorg, Joseph A.;Blaylock, Bill;Schneewind, Olaf
III 型耶尔森氏菌机器跨细菌包膜分泌蛋白质底物。一些底物的分泌信号已被鉴定；然而，这些信号与 III 型机器相互作用的机制尚不清楚。在这里，我们表明，早期分泌底物 YopR 与二氢叶酸还原酶 (DHFR) 或其他紧密折叠蛋白的 IN 末端融合，会产生无法通过 III 型途径的不可通过的杂合体。 YopR 杂交体捕获 YscN，这是细菌细胞质中为 III 型转运反应提供能量的 ATP 酶。 11 个 IN 末端残基充当 YopR 分泌信号，这是与 YscN 结合和阻断 III 型途径所必需的。当在 III 型机器组装过程中表达时，YopR-DHFR 会阻止所有分泌。当耶尔森菌已经参与 III 型途径时，YopR-DHFR 的延迟表达会阻止早期 (YscP) 底物的分泌，但不会阻止晚期（效应子 Yops）底物的分泌。这些观察结果支持了一个模型，根据该模型，III 型机器被编程为分泌一系列蛋白质，当不可通过的早期底物与 YscN ATP 酶相互作用并阻止晚期底物的运输时，这些蛋白质序列就会被破坏。
Yersinia type III machines secrete protein substrates across the bacterial envelope. Secretion signals of some substrates have been identified; however, the mechanisms whereby these signals interact with type III machines are not known. Here we show that fusion of YopR, an early secretion substrate, to the IN terminus of dihydrofolate reductase (DHFR) or other tightly folded proteins generates impassable hybrids that cannot travel the type III pathway. YopR hybrids capture YscN, the ATPase that provides energy for type III transport reactions, in the bacterial cytoplasm. Eleven IN-terminal residues function as the YopR secretion signal, which is required for both binding to YscN and blocking the type III pathway. When expressed during type III machine assembly, YopR-DHFR blocks all secretion. Delayed expression of YopR-DHFR, when yersiniae have already engaged the type III pathway, blocks secretion of early (YscP) but not of late (effector Yops) substrates. These observations support a model whereby type III machines are programmed to secrete a sequence of proteins that can be disrupted when an impassable early substrate interacts with the YscN ATPase and blocks the transport of late substrates.