通过细菌效应剂独立于E1和E2酶的化
Jiazhang Qiu1, Michael J Sheedlo2, Kaiwen Yu3
1Purdue Institute for Inflammation, Immunology and Infectious Disease and Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
Nature
|April 7, 2016
概括
细菌病原体如雷吉欧内拉肺使用新型酶来无处不在的宿主蛋白质. 这一过程绕过了传统的E1/E2酶,只需要尼古丁胺氨基二核酸来激活全方位.
科学领域:
- 细胞生物学
- 微生物学
- 生物化学
背景情况:
- 化是一种关键的转化后修饰,调节真核细胞过程.
- 规范的泛素化途径涉及三种酶级联:E1,E2和E3.
- 传染病常常针对无处不在网络进行生存和复制.
研究的目的:
- 调查Legionella pneumophila效应体对宿主位的机制.
- 确定细菌的无处不在活性是否需要宿主的E1和E2酶.
- 阐明特定动机在细菌效应器介导的无处不在中的作用.
主要方法:
- 标识和描述Legionella pneumophila的Side家族效应体.
- 在实验室中使用细菌效应剂,全方位和各种基质 (例如Rab GTPases) 进行全方位测试.
- 酶活性测定以评估对E1,E2酶,ATP和尼古丁胺氨基二核酸 (NAD) 的需求.
- 在SIDE效应器中对假定单-ADP-ribosyltransferase基因的突变分析.
- 在原生动物宿主体内进行细胞内复制测试,以评估Side效应器的体内功能.
主要成果:
- 雷吉欧内拉肺Side家族的效应者在宿主Rab小GTPases中存在.
- 这些细菌效应剂独立于宿主E1和E2酶催化泛化.
- 一个保存的单-ADP-ribosyltransferase动机对于Side效应器的无处不在活性至关重要.
- 独立于E1/E2的泛素化反应由尼古丁胺氨基二核酸 (NAD) 驱动,形成ADP-ribosylated泛素.
- 在原生动物宿主中,Side的无处不在活性对细胞内细菌的复制至关重要.
结论:
- 可由单个酶催化,独立于正规的E1/E2级联.
- 菌利用一种新的E1/E2独立的无处不在机制来操纵宿主细胞.
- 这种细菌策略突显了无处不在的途径的适应性和病原体的利用.
- 这些发现揭示了一种全方位基因修饰的新模式,对理解宿主-病原体相互作用和基本的全方位基因生物学的潜在影响.
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