通过空间障碍,PSGL-1将HIV Env排除在 virion 表面之外,其中包括十倍重复 (DR) 的结构折叠
Sameer Tiwari1, Bryan M Delfing2, Yang Han1
1Center for Infectious Disease Research, George Mason University, Manassas, VA 20110, USA.
bioRxiv : the preprint server for biology
|January 7, 2025
概括
通过防止病毒Env的结合,P-选择蛋白糖蛋白连接体-1 (PSGL-1) 阻断了HIV. 它的细胞外十倍重复,形成一个状结构,对于这种HIV限制机制至关重要.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- P-选择蛋白糖蛋白连接体-1 (PSGL-1) 是一种在免疫细胞上发现的细胞表面糖蛋白.
- PSGL-1 作为一种HIV限制因子,抑制病毒感染性.
- 之前,PSGL-1将HIV Env从病毒中排除的机制尚不清楚.
研究的目的:
- 为了研究PSGL-1-介导的HIV Env排除的分子机制.
- 确定PSGL-1的细胞外 (EC) 和细胞内 (IC) 域在Env排除中的作用.
主要方法:
- 删除PSGL-1的EC和IC域的突变发生.
- 对PSGL-1在Env合并中的十倍重复 (DR) 函数的分析.
- 分子建模用于预测PSGL-1突变体的结构变化.
主要成果:
- 对于PSGL-1的Env排除活动来说,EC和IC领域都很重要.
- 删除EC域取消了Env排除,而IC域删除部分减少了它.
- 对于有效的Env排除,在EC域中至少需要9个decameric重复 (DR),更少的DR导致了一个未能排除Env的扩展结构.
结论:
- PSGL-1的Env排除活动依赖于其结构构造,特别是由至少9个DR构成的卷状结构.
- 这种结构特征在空间上阻碍了HIV Env在组装病毒中融入.
- 这些发现阐明了一种由PSGL-1独特的结构性质介导的HIV限制的新机制.
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