Nitric oxide inhibits the cochaperone activity of the RING finger-like protein DnaJ
Nitric oxide inhibits the cochaperone activity of the RING finger-like protein DnaJ
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DOI：
10.1006/niox.2001.0354
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发表时间：
2001-08-01
影响因子：
3.9
通讯作者：
Hayer-Hartl, MK
中科院分区：
文献类型：
--
作者：
Kröncke, KD;Haase, H;Hayer-Hartl, MK
作为细菌感染和随后的炎症的结果，诱导型NO合酶的表达导致高浓度NO的延长合成，这在其他功能中有助于对感染因子的先天防御。在这里，我们表明，NO抑制的能力，细菌cochaperone DnaJ含有一个环指状结构域合作与热休克蛋白70分子伴侣DnaK介导的正确折叠变性罗丹。这种抑制伴随着DnaJ的S-亚硝化以及从蛋白质中释放Zn 2+。相反，NO对GroEL的活性没有影响，GroEL是一种没有锌硫簇的细菌伴侣。大肠杆菌细胞缺乏伴侣触发因子，因此依赖于DnaJ/DnaK系统更容易对NO介导的细胞停滞比野生型细菌。我们的研究确定了cochaperone DnaJ作为NO的分子靶点。因此，遇到细菌细胞与NO可以损害细菌分子伴侣系统的蛋白质折叠活性，从而增加细菌对宿主防御攻击的易感性。(C)北京：科学出版社.
As a consequence of bacterial infection and the ensuing inflammation, expression of the inducible NO synthase results in prolonged synthesis of NO in high concentrations, which among other functions, contributes to the innate defense against the infectious agent. Here we show that NO inhibits the ability of the bacterial cochaperone DnaJ containing a RING finger-like domain to cooperate with the Hsp70 chaperone DnaK in mediating correct folding of denatured rhodanese. This inhibition is accompanied by S-nitrosation of DnaJ as well as by Zn2+ release from the protein. In contrast, NO has no effect on the activity of GroEL, a bacterial chaperone without zinc sulfur clusters. Escherichia coli cells lacking the chaperone trigger factor and thus relying on the DnaJ/DnaK system are more susceptible toward NO-mediated cytostasis than are wildtype bacteria. Our studies identify the cochaperone DnaJ as a molecular target for NO. Thus, an encounter of bacterial cells with NO can impair the protein folding activity of the bacterial chaperone system, thereby increasing bacterial susceptibility toward the defensive attack by the host. (C) 2001 Academic Press.