对HBV受体和胆酸载体NTCP的结构洞察
Jae-Hyun Park1, Masashi Iwamoto2, Ji-Hye Yun3,4
1Drug Design Laboratory, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.
Nature
|May 17, 2022
概括
乙型肝炎病毒 (HBV) 使用甲酸共运输多 (NTCP) 受体感染肝细胞. 科学家们解决了NTCP的结构,
科学领域:
- 结构生物学
- 病毒学
- 肝病学
背景情况:
- 全球大约有2.5亿人感染乙型肝炎病毒 (HBV).
- 肝炎D病毒 (HDV) 同感染会增加严重肝病的风险.
- 甲酸共运输聚 (NTCP) 是HBV进入的鉴定受体.
研究的目的:
- 确定人类NTCP传送器的三维结构.
- 阐明HBV与NTCP相互作用的结构基础.
- 确定抗病毒药物设计的潜在目标.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来解决NTCP结构.
- 通过结合抗体来确定NTCP的结构.
- 与相关的溶质载体家族10 (SLC10) 蛋白进行了比较分析.
主要成果:
- NTCP的冷EM结构已经成功解决.
- 在其他SLC10蛋白中,NTCP缺乏第一个跨膜螺旋.
- 在NTCP细胞外面发现了一种与HBV preS1域相互作用的独特口袋.
结论:
- 解决的NTCP结构为胆酸运输机制提供了洞察力.
- 已确定的preS1相互作用口袋为开发HBV疗法提供了一个新的目标.
- 可以探索基于结构的药物设计策略来抑制HBV的进入.
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