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Updated: Jan 6, 2026

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简单疹起源结合蛋白:由Cryo-EM揭示的特定序列DNA结合和二元化机制

Emil Gustavsson^1,2, Kay Grünewald^2,3,4, Per Elias⁵

¹Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm 171 77, Sweden.

Nucleic acids research

|October 22, 2025

概括

新的冷EM结构揭示了疹病毒-1原始结合蛋白 (OBP) 如何识别DNA. 这些发现确定了抗病毒药物对抗耐药性简单疹病毒的潜在新目标.

科学领域:

结构生物学结构生物学
病毒学病毒学
药物发现药物发现药物发现

背景情况:

简单疹病毒 (HSV-1,2) 对当前的抗病毒疗法具有越来越强的抗药性.
HSV-1起源结合蛋白 (OBP) 是一种DNA螺旋酶,是新的抗病毒药物的潜在目标.

研究的目的:

确定HSV-1 OBP与DNA和ATP类似物复合的结构.
阐明HSV-1DNA起源识别和解的分子机制.
在HSV-1 OBP上识别潜在的药物可用部位,用于抗病毒药物开发.

主要方法:

低温电子显微镜 (cryo-EM) 在高达2.8 Å的分辨率.
在多个构造状态下对OBP进行结构分析,包括具有OriS DNA和ATPγS的复合体.
调查OBP-DNA相互作用,包括单体-DNA和二元-二元组件.

主要成果:

揭示了一个意想不到的头到尾的OBP二极管结构,由C端域稳定.
确定RVKNL基因对特定序列DNA识别至关重要.
发现了OBP和ICP8.8之间潜在的监管相互作用.
观察到OBP单体与DNA发针结合,以及与DNA结合的二次二次组合.

结论:

这些结构为HSV-1起源识别和解提供了分子洞察力.
在OBP上识别了多个可使用药物的接口,用于基于结构的抗病毒设计.
铺平了开发新型抗病毒药物抗药性HSV-1感染的道路.

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