Rack Johannes Gregor Matthias, Morra Rosa, Barkauskaite Eva, Kraehenbuehl Rolf, Ariza Antonio, Qu Yue, Ortmayer Mary, Leidecker Orsolya, Cameron David R, Matic Ivan, Peleg Anton Y, Leys David, Traven Ana, Ahel Ivan
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
Mol Cell. 2015 Jul 16;59(2):309-20. doi: 10.1016/j.molcel.2015.06.013. Epub 2015 Jul 9.
Sirtuins are an ancient family of NAD(+)-dependent deacylases connected with the regulation of fundamental cellular processes including metabolic homeostasis and genome integrity. We show the existence of a hitherto unrecognized class of sirtuins, found predominantly in microbial pathogens. In contrast to earlier described classes, these sirtuins exhibit robust protein ADP-ribosylation activity. In our model organisms, Staphylococcus aureus and Streptococcus pyogenes, the activity is dependent on prior lipoylation of the target protein and can be reversed by a sirtuin-associated macrodomain protein. Together, our data describe a sirtuin-dependent reversible protein ADP-ribosylation system and establish a crosstalk between lipoylation and mono-ADP-ribosylation. We propose that these posttranslational modifications modulate microbial virulence by regulating the response to host-derived reactive oxygen species.
沉默调节蛋白是一个古老的烟酰胺腺嘌呤二核苷酸（NAD⁺）依赖性脱酰基酶家族，与包括代谢稳态和基因组完整性在内的基本细胞过程的调节有关。我们发现了一类迄今为止未被认识的沉默调节蛋白，主要存在于微生物病原体中。与先前描述的类别不同，这些沉默调节蛋白表现出强大的蛋白质ADP-核糖基化活性。在我们的模式生物金黄色葡萄球菌和化脓性链球菌中，该活性依赖于靶蛋白先前的硫辛酰化，并且可以被一种与沉默调节蛋白相关的宏结构域蛋白逆转。总之，我们的数据描述了一个依赖于沉默调节蛋白的可逆蛋白质ADP-核糖基化系统，并建立了硫辛酰化和单ADP-核糖基化之间的相互作用。我们提出，这些翻译后修饰通过调节对宿主衍生的活性氧的反应来调节微生物毒力。
