艾滋病毒体的核孔通道是由其不寻常的表面氨基酸组成驱动的
Liran Fu1, Shiya Cheng2,3, Dietmar Riedel4
1Department of Cellular Logistics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Nature structural & molecular biology
|October 9, 2025
概括
人类免疫缺陷病毒 (HIV) 囊体模仿核运输受体 (NTRs) 进入细胞核. 它们的表面特性,而不仅仅是结合口袋,促进通过核孔综合体 (NPC) 的通行.
科学领域:
- 细胞生物学 细胞生物学
- 病毒学 病毒学
- 生物物理学的生物物理.
背景情况:
- 核孔复合体 (NPC) 调节细胞质和核之间的运输.
- 核运输受体 (NTR) 促进货物通过NPC通过.
- 人类免疫缺陷病毒 (HIV) 囊体进入非分裂细胞的细胞核,绕过正常的载荷通路.
研究的目的:
- 阐明HIV体与NPC相互作用并穿越的分子机制.
- 识别特定的体特征,使其作为NTR的行为.
主要方法:
- 对体表面特性进行分析,重点关注氨基酸成分和电荷.
- 调查FG重复域在NPC中的作用.
- 评估改变体表面残留物对NPC相互作用和通过的影响.
主要成果:
- 艾滋病毒囊的外表面,而不是特定的结合口袋,对于NPC通道至关重要.
- 体表面残留物缺乏FG排斥性电荷 (K,D,E),而是具有FG吸引性残留物.
- 修改体表面以包括FG排斥残留物可以抑制NPC的向和通过.
- 通过表面侧链介导的过渡性FG吸引性相互作用使体在NPC的FG阶段变得可溶.
结论:
- 艾滋病毒体利用它们的表面特性来模仿NTRs,使其能够有效地进入核.
- 囊体的表面组成决定了它与NPC的FG相屏障的相互作用.
- CPSF6可以通过掩盖有吸引力的相互作用和诱导排斥来调节NPCs的囊体释放.
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