EspH利用酸和Rab结合域与血感染部位和Rab GTPases相互作用
Ipsita Nandi1,2, Rachana Pattani Ramachandran1,2, Deborah E Shalev3,4
1Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, The Edmond J. Safra Campus - Givat Ram, Jerusalem, Israel.
肠道病原性大肠杆菌 (EPEC) 使用 EspH 效应器通过与 Rab GTPases 相互作用来破坏宿主细胞过程. 这种互动对EPEC至关重要.
科学领域:
- 微生物学 微生物学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 肠病原性大肠杆菌 (EPEC) 是持续性腹的一个重要原因.
- EPEC 将效应蛋白注入宿主细胞,以操纵细胞功能.
- 了解效应因子机制是对抗EPEC感染的关键.
研究的目的:
- 为了阐明由EPEC效应蛋白 EspH.介导的宿主-病原体相互作用.
- 为了确定 EspH 中涉及病毒性的特定宿主因素和域.
主要方法:
- 使用AlphaFold进行结构预测.
- 采用位点定向突变发生法来探测 EspH 功能.
- 进行了Rab8a.的基因淘汰实验.
- 研究了蛋白质-蛋白质相互作用和细胞局部化.
主要成果:
- EspH与多个宿主Rab GTPases相互作用,其特定残留物 (Glu37,Lys41) 对于结合至关重要.
- 这些残留物中的突变取消了 EspH 抑制 Akt/mTORC1 信号传递,溶酶体外细胞和细菌入侵的能力.
- Rab8a在Akt/mTORC1信号传递和溶酶体外细胞分裂中发挥作用.
- 在EspH中,包括关键的氨酸在内的氨酸结合域对于Rab相互作用和在感染部位的定位至关重要.
结论:
- 确定了新的EspH-Rab GTPase相互作用,这些相互作用对EPEC病变产生至关重要.
- 证明了特定的EspH残留物和氨酸化物结合域在毒性中的作用.
- 揭示了在EPEC感染期间影响宿主免疫信号和膜贩运的ESPH依赖机制.
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