具有广泛中和抗体PG9的HIV-1 gp120 V1/V2域的结构
Jason S McLellan1, Marie Pancera, Chris Carrico
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nature
|November 25, 2011
概括
人类免疫缺陷病毒-1 (HIV-1) 包裹V1/V2区域是免疫逃避的关键. 研究人员确定了V1/V2与PG9抗体结合的结构,揭示了一个新的中和机制.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 结构生物学 结构生物学
背景情况:
- 艾滋病毒-1 gp120包膜糖蛋白的可变区域1和2 (V1/V2) 对于病毒免疫逃避至关重要.
- 这些区域受到高序列多样性和N-链糖化保护,这对抗体中和构成了挑战.
研究的目的:
- 确定HIV-1 V1/V2区域与中和抗体PG9.9复合的结构.
- 阐明PG9等抗体通过V1/V2区域识别和中和HIV-1的机制.
主要方法:
- 使用X射线结晶学来确定V1/V2-PG9复合物的结构.
- 使用结构分析来描述V1/V2,甘氨酸和抗体之间的相互作用.
主要成果:
- V1/V2区域形成一个四链β片域,其多样性和糖化定位为循环.
- PG9的识别涉及静电,序列独立和甘氨酸相互作用,甘氨酸对结合表面有显著的贡献.
- 抗体CH04和PGT145共享一个共同的糖透机制,涉及离子环.
结论:
- 该研究从结构上定义了HIV-1 V1/V2区域及其与中和抗体的相互作用.
- 确定了高度甘化抗原的抗体识别范式,突出了V1/V2区域的脆弱性,涉及特定的甘和β-sheet链.
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Antibodies consist of four polypeptide chains: two identical heavy...
01:10Antibody Structure
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Antibodies, also known as immunoglobulins (Ig), are essential players of the adaptive immune system. These antigen-binding proteins are produced by B cells and make up 20 percent of the total blood plasma by weight. In mammals, antibodies fall into five different classes, which each elicits a different biological response upon antigen binding.
The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
Antibodies consist of four polypeptide chains: two identical heavy...
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The Y-Shaped Structure of Antibodies Consists of Four Polypeptide Chains
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