三重性HIV-1-Env结构定义了A,B和G类的糖盾
Guillaume B E Stewart-Jones1, Cinque Soto1, Thomas Lemmin2
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Cell
|April 27, 2016
概括
艾滋病毒-1封面 (Env) 剪切器
科学领域:
- 结构生物学
- 免疫学
- 病毒学
背景情况:
- 人类免疫缺陷病毒1型 (HIV-1) 包裹 (Env) 片被密集的N-链 glycans覆盖.
- 这种甘氨酸屏蔽对于HIV-1逃避宿主体内免疫力至关重要.
- 了解甘氨酸屏蔽的结构是开发有效的HIV-1疗法的关键.
研究的目的:
- 为了阐明HIV-1糖盾的结构组织.
- 调查糖盾如何促进HIV-1免疫逃逸.
- 识别可被广泛中和抗体准的糖盾的特征.
主要方法:
- 来自A,B和G基团的完全糖化HIV-1 Env三角体的结晶.
- 高分辨率 (3.4-3.7 Å) 结构分析Env和其糖屏蔽.
- 糖-阵列结合测试和分子动力学模拟.
主要成果:
- 艾滋病毒-1 糖盾形成了一个由糖拥挤驱动的相互锁定的寡糖化合物的有序网络.
- 这种密集的屏蔽包围了Env蛋白,有效地阻断了大多数抗体介导的中和.
- 在盾牌内确定了N-链接的甘氨酸-甘氨酸相互作用的分类法,其中有序,保存和处理的变化.
- 在针对Env三元体的广泛中和抗体中观察到寡糖类多样性和适应甘氨酸的需求.
结论:
- 对有序的糖盾的结构洞察力为了解HIV-1免疫逃避提供了一个框架.
- 这一发现突显了HIV-1的防御机制中的甘氨酸与蛋白质之间的复杂相互作用.
- 了解甘-甘相互作用和抗体适应对于设计下一代HIV-1疫苗和治疗药物至关重要.
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