通过卡尔莫杜林依赖的谷氨基酶调节基基化
Ninghai Gan1, Xiangkai Zhen2,3, Yao Liu1
1Purdue Institute for Inflammation, Immunology and Infectious Disease and Department of Biological Sciences, Purdue University, West Lafayette, IN, USA.
Nature
|July 23, 2019
概括
菌使用效应剂SidJ来抑制细菌的毒性因素. SidJ将谷氨酸连接到SdeA,这一过程需要宿主卡尔莫杜林,揭示了一个新的宿主因子依赖的调节机制.
科学领域:
- 微生物学
- 分子生物学
- 生物化学
背景情况:
- 使用Dot/Icm效应器调节宿主细胞.
- 通过独特的基化,Side家族蛋白调节细胞过程.
- SidJ是一种调节Side活动的Dot/Icm效应器,但其机制尚不清楚.
研究的目的:
- 阐明SidJ调节Side家族效应器的机制.
- 研究宿主因素在SidJ调节中的作用.
- 描述SidJ活动的结构和生化基础.
主要方法:
- 位点定向的突变生成以确定催化残留物.
- 结构生物学 (X射线晶体学) 来确定复杂的结构.
- 生物化学测试以评估酶活性和基质修饰.
主要成果:
- 通过催化SdeA在一个关键的催化残留物 (E860) 中的化,SidJ抑制了SideE的活性.
- 它的活性依赖于宿主蛋白质calmodulin (CaM),其功能仅限于真核细胞.
- 在没有谷氨酸或SdeA的情况下,SidJ表现出使用ATP的自我AMPylation活动,涉及α-酸盐的分裂.
结论:
- SidJ采用宿主因子依赖的谷氨基化机制来抑制细菌毒性因子.
- 这一发现揭示了细菌致病的新型调节途径,涉及宿主因子的激活.
- 这些发现提供了细菌效应器和宿主细胞机制之间的复杂相互作用的见解.
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