多种肠道病原体通过一种保存的机制利用宿主吞途径
Mahitha Shree Anandachar1, Suchismita Roy2, Saptarshi Sinha2
1Department of Cellular and Molecular Medicine, University of California San Diego, San Diego, California, USA; Department of Pathology, University of California San Diego, San Diego, California, USA.
The Journal of biological chemistry
|October 27, 2023
概括
病原体使用效应蛋白来逃避宿主防御. 研究人员确定了这些效应因子准的关键宿主蛋白相互作用部位,揭示了可以用于新疗法的漏洞.
科学领域:
- 细胞微生物学 细胞微生物学
- 宿主-病原体相互作用
- 分子免疫学分子免疫学
背景情况:
- 巨细胞吞了病原体的phagolysosomes,这是一个关键的防御机制.
- 病原体使用具有WxxxE动机的效应蛋白来破坏宿主细胞功能并建立细胞内.
- 了解这些分子相互作用是对抗传染病的关键.
研究的目的:
- 为了识别病原体WxxxE效应器所准的宿主蛋白质.
- 阐明效应体与宿主蛋白结合的分子机制.
- 研究破坏这种相互作用的功能后果.
主要方法:
- 同性学建模和局部定向突变发生,以确定结合部位.
- 蛋白质与蛋白质相互作用网络分析.
- 在状网络中扰动和宿主细胞中的功能测试.
主要成果:
- 在ELMO1 (吞和细胞流动性蛋白1) 上,一个保存的"热点"PH域与多种WxxxE效应器结合.
- 在ELMO1上的一种氨酸三合一直接与SifA,IpgB1,IpgB2和Map相互作用.
- 破坏SifA-ELMO1相互作用会减少Rac1的活动和微生物入侵.
结论:
- ELMO1效应器接口代表了病原体颠覆策略的融合点.
- 这种接口是病原体和宿主之间共同进化的分子适应的一个关键位置.
- 针对这种接口提供了针对各种细菌感染的潜在治疗策略.
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