微管脱聚合的结构基础由HIV-1 Rev的基因素类活性
Elif Eren1, Norman R Watts1, Davide Randazzo2
1Protein Expression Laboratory, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Structure (London, England : 1993)
|August 12, 2023
概括
艾滋病毒-1 Rev蛋白与蛋白结合,形成一个使微管不稳定的复合物. 这种相互作用揭示了Rev在调节宿主细胞中的新角色.
科学领域:
- 结构生物学 结构生物学
- 病毒学 病毒学
- 细胞生物学 细胞生物学
背景情况:
- 人类免疫缺陷病毒1型 (HIV-1) Rev蛋白对病毒基因表达至关重要.
- Rev促进病毒mRNA从细胞核到细胞质的运输.
- Rev 与宿主蛋白相互作用,劫持病毒复制的细胞机械.
研究的目的:
- 确定HIV-1 Rev和宿主细胞组件之间的相互作用的结构基础.
- 阐明Rev-tubulin复合体在细胞过程中的作用.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于以3.5 Å分辨率确定Rev-tubulin环复合物的结构.
- 生物化学测试评估了Rev-tubulin相互作用对微管体稳定性的影响.
- 在星体细胞和HeLa细胞中进行的细胞表达研究研究了Rev对微管细胞骨架的影响.
主要成果:
- 4.8 MDa的Rev-tubulin环复合结构揭示了Rev的氨酸丰富基因 (ARM) 与α/β-tubulin的酸性表面和C端尾部结合.
- Rev-tubulin相互作用在亚静态度度下强烈破坏微管的稳定,在功能上模仿kinesin-13.
- 细胞中的Rev表达调节了微管细胞骨架.
结论:
- 艾滋病毒-1Rev直接与蛋白相互作用,形成一个使微管不稳定的复合物.
- 这种相互作用表明Rev在mRNA传输之外的前所未有的调节功能.
- Rev调节宿主细胞的微管细胞骨架的能力可能在病毒病原发生过程中发挥作用.
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