对ISG15的USP18特异性的机制通过并行序列分析比较分析揭示出来
Thomas Bonacci1, Derek L Bolhuis2, Nicholas G Brown1
1Department of Pharmacology and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
The Journal of biological chemistry
|May 28, 2025
概括
酶USP18去除蛋白质ISG15,这对于控制干扰素信号传递和对抗感染至关重要. 研究人员确定了USP18的关键特征,负责这种特定的去ISGylating活动.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 干扰素刺激的15基因 (ISG15) 结合调节宿主对病原体的防御.
- ISG15通过全胺特异蛋白酶18 (USP18) 的解对于控制干扰素信号传递至关重要.
- 对USP18对ISG15的特异性的分子基础尚不清楚.
研究的目的:
- 阐明USP18的脱化活性和ISG15特异性的分子决定因素.
- 将USP18与其同类USP41进行比较,该USP41缺乏deISGylating功能.
主要方法:
- 对USP18和USP41进行比较序列分析.
- 生物化学和酶学测定以评估去ISGylating活动.
- 用AlphaFold引导的结构分析来预测蛋白质相互作用.
主要成果:
- 在USP18中确定了对ISG15识别和水解至关重要的特定序列特征.
- 这些特征在非deISGylating类比USP41.1.中不存在.
- 结构分析表明,这些特征介于USP18-ISG15相互作用.
结论:
- 揭示了对USP18介导的ISG15水解的机械洞察力.
- 识别的特征对于USP18的酶功能和基质特异性至关重要.
- 这些发现可能有助于开发用于传染病和干扰素相关疾病的deISGylase抑制剂.
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