通过HIV-1封面尖峰识别的结构基础
Md Munan Shaik1,2, Hanqin Peng1, Jianming Lu3,4
1Division of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Nature
|December 14, 2018
概括
艾滋病毒-1包膜糖蛋白 (Env) 结构揭示了CCR5核受体结合如何破坏gp41的稳定,从而启动病毒融合. 这一发现澄清了艾滋病毒的进入机制,
科学领域:
- 结构生物学
- 病毒学
- 免疫学
背景情况:
- 艾滋病毒-1的进入依赖于包膜糖蛋白 (Env) 与CD4和CCR5等共受体的相互作用.
- 通过gp41触发病毒融合,gp120核受体的结合至关重要.
- 了解这种相互作用对于开发HIV治疗和疫苗至关重要.
研究的目的:
- 确定与CD4和CCR5复合的HIV-1 gp120的高分辨率结构.
- 阐明CCR5结合启动病毒融合的分子机制.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来获得3.9 Å的分辨率结构.
- 这项研究分析了全长gp120,可溶性CD4和未修改的人类CCR5之间的相互作用.
主要成果:
- 在gp120的V3循环插入到CCR5的化学结口袋.
- 结合CCR5不会导致gp120的异质变化,但会使Env更接近目标膜.
- Gp120的N端翻转,可能会破坏gp41的稳定并启动融合.
结论:
- 在细胞膜附近,CCR5 作为 CD4 结合的 Env 形状的稳定.
- 这些发现提供了有关HIV-1入境途径的关键见解.
- 这种结构理解可能会为新型艾滋病毒疫苗和治疗方法的设计提供信息.
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