HCMV US2 选择了 TRC8 来降解内细胞网膜居住蛋白质 LMAN2L
Leah M Hunter1,2, Joanne Kite1,2, Alice Fletcher-Etherington1,2
1Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
The Journal of general virology
|April 30, 2024
概括
人类细胞巨型病毒 (HCMV) 蛋白pUS2降解了像 (LMAN2L) 这样结合2的莱克曼诺,以间接降低细胞表面的整合素α-6 (ITGA6). 这揭示了HCMV免疫逃避的双重机制.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 人类细胞巨化病毒 (HCMV) 蛋白pUS2通过ER相关降解 (ERAD) 途径向宿主蛋白进行降解.
- HCMV pUS2降低了主要组织相容性复合物I类 (MHC-I),以逃避免疫检测.
- pUS2还准其他细胞蛋白,影响它们的细胞表面表达.
研究的目的:
- 为了识别HCMV pUS2.2.的新型细胞点.
- 研究pUS2影响细胞表面蛋白质表达的机制.
- 阐明LMAN2L在pUS2介导的蛋白质下调中的作用.
主要方法:
- 蛋白质分子等离子膜分析被用来识别细胞表面的变化.
- 对LMAN2L和ITGA6的表达水平进行了分析,在pUS2.2的存在和缺乏的情况下进行了分析.
- 评估了LMAN2L降解对E3结合酶TRC8的依赖性.
主要成果:
- 确定了一种新的pUS2标,即类似于 (LMAN2L) 的莱克曼诺结合2 (LMAN2L).
- 通过pUS2介导的LMAN2L下调是依赖于E3结合酶TRC8.8的.
- 由于LMAN2L缺乏,导致细胞表面的整合素α-6 (ITGA6) 的下调.
结论:
- HCMV pUS2采用一种新的间接机制,通过向LMAN2L进行降解来降低ITGA6的调节.
- 这种间接途径补充了pUS2已知的直接向其他细胞表面分子的途径.
- HCMV利用直接和间接的策略来调节宿主细胞表面蛋白质以逃避免疫.
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