Christensen Susanne K, Pedersen Kim, Hansen Flemming G, Gerdes Kenn
Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark.
J Mol Biol. 2003 Sep 26;332(4):809-19. doi: 10.1016/s0022-2836(03)00922-7.
Prokaryotic chromosomes encode toxin-antitoxin loci, often in multiple copies. In most cases, the function of these genes is not known. The chpA (mazEF) locus of Escherichia coli has been described as a cell killing module that induces bacterial apoptosis during nutritional stress. However, we found recently that ChpAK (MazF) does not confer cell killing but rather, induces a bacteriostatic condition from which the cells could be resuscitated. Results presented here yield a mechanistic explanation for the detrimental effect on cell growth exerted by ChpAK and the homologous ChpBK protein of E.coli. We show that both proteins inhibit translation by inducing cleavage of translated mRNAs. Consistently, the inhibitory effect of the proteins was counteracted by tmRNA. Amino acid starvation induced strong transcription of chpA that depended on Lon protease but not on ppGpp. Simultaneously, ChpAK cleaved tmRNA in its coding region. Thus, ChpAK and ChpBK inhibit translation by a mechanism very similar to that of E.coli RelE. On the basis of these results, we propose a model that integrates TA loci into general prokaryotic stress physiology.
原核生物染色体编码毒素 - 抗毒素基因座，通常有多个拷贝。在大多数情况下，这些基因的功能尚不清楚。大肠杆菌的chpA（mazEF）基因座被描述为一个细胞杀伤模块，在营养应激期间诱导细菌凋亡。然而，我们最近发现ChpAK（MazF）并不导致细胞死亡，而是诱导一种抑菌状态，细胞可以从中复苏。本文给出的结果对ChpAK和大肠杆菌同源的ChpBK蛋白对细胞生长产生的有害影响提供了一个机制性解释。我们表明这两种蛋白通过诱导已翻译的mRNA的切割来抑制翻译。一致地，tmRNA抵消了这些蛋白的抑制作用。氨基酸饥饿诱导chpA的强烈转录，这依赖于Lon蛋白酶而不依赖于ppGpp。同时，ChpAK在其编码区域切割tmRNA。因此，ChpAK和ChpBK通过一种与大肠杆菌RelE非常相似的机制抑制翻译。基于这些结果，我们提出了一个将毒素 - 抗毒素基因座整合到一般原核生物应激生理学中的模型。
