与LDLRAD3受体复合的委内瑞拉马类脑炎病毒的结构
Katherine Basore1, Hongming Ma2, Natasha M Kafai1,2
1Department of Pathology & Immunology, Washington University School of Medicine, St Louis, MO, USA.
Nature
|October 14, 2021
概括
研究人员确定LDLRAD3是委内瑞拉马脑炎病毒 (VEEV) 的受体. 结构分析揭示了VEEV如何结合LDLRAD3,为开发新的α病毒疗法提供了洞察力.
科学领域:
- 病毒学
- 结构生物学
- 免疫学
背景情况:
- 委内瑞拉马脑炎病毒 (VEEV) 是一种导致人类严重神经疾病的新世界阿尔法病毒.
- 已确定LDLRAD3是VEEV的关键附着和入口受体.
研究的目的:
- 确定VEEV及其与LDLRAD3复合物的近原子分辨率结构.
- 阐明VEEV与LDLRAD3结合的分子机制.
主要方法:
- 用冷电子显微镜 (cryo-EM) 来重建类似VEEV病毒的粒子和VEEV-LDLRAD3复合体.
- 突变性研究和抗VEEV抗体结合竞争试验以验证结合界面.
主要成果:
- 获得了VEEV及其与LDLRAD3ectodomains复合物的近原子分辨率结构.
- LDLRAD3域1通过插入尖端内由E2-E1异构体形成的裂来结合VEEV.
- VEEV-LDLRAD3接口在结构上类似,但比其他alphavirus与各自的受体形成的接口更小.
结论:
- 这项研究提供了VEEV-LDLRAD3相互作用的详细结构理解.
- 这种知识可以帮助开发针对阿尔法病毒感染的广泛疗法.
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