通过smFRET观察到的HIV-1包膜糖蛋白结构与病毒状态的关联
Maolin Lu1, Xiaochu Ma1, Luis R Castillo-Menendez2,3
1Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.
Nature
|April 12, 2019
概括
高分辨率的HIV- 1 Env三元体结构不代表预触发状态. 目前的结构模型主要显示中间或CD4结合的结构,使预触发状态结构未知.
科学领域:
- 结构生物学
- 病毒学
- 免疫学
背景情况:
- 艾滋病毒-1包膜糖蛋白 (Env) 三分体对于病毒的进入至关重要,并表现出形态动态.
- 之前的结构研究使用了稳定SOSIP.664或Env-Cryo-EM复合体,产生了类似的结构.
- 这些结构被认为代表了Env的预触发状态 (状态1),但这仍然未经测试.
研究的目的:
- 在结构研究中使用的Envtrimers与原生Env在完整的HIV-1病毒的构造状态进行比较.
- 为了确定现有的高分辨率结构是否准确地代表了HIV-1 Env的预触发形状.
主要方法:
- 使用单分子光共振能量转移 (smFRET) 成像.
- 在完整的病毒体上分析了原生Env的构造状态.
- 在结构研究中使用的Env形与原生Env形进行比较.
主要成果:
- 用于结构研究的Env剪裁器主要采用下游构造 (状态2和3).
- 这些形状代表了中间状态或CD4结合状态,而不是预触发状态 (状态1).
- 原生,预触发的HIV-1 Env形状的结构仍未确定.
结论:
- 现有的HIV-1 Env高分辨率结构不代表生物相关的预触发状态.
- 预触发Env状态的未知结构是设计免疫原体和开发治疗方法的关键缺口.
- 需要进一步研究以确定预触发的Env构造的结构.
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