AcrDB更新:预测人类肠道病毒组中的反CRISPRs的3D结构
Minal Khatri1, N R Siva Shanmugam1, Xinpeng Zhang1
1Nebraska Food for Health Center, Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
概括
这项研究引入了更新的Anti-CRISPR数据库 (AcrDB),其中包括来自肠道病毒的预测结构和新的结构搜索功能. 它确定了795个候选Acrs,推动了基因组编辑和菌体与宿主相互作用研究.
科学领域:
- 基因组学和生物信息学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 反CRISPR (Acr) 蛋白在菌体与宿主相互作用中至关重要,并有可能用于基因组编辑.
- 由于序列相似性较低,发现新型Acrs受到阻碍,需要使用替代的识别方法.
- 蛋白质结构预测的进步为Acr通过结构比较的发现提供了新的途径.
研究的目的:
- 更新和增强Anti-CRISPR数据库 (AcrDB) 以新的功能来改进Acr发现.
- 使用先进的结构预测工具,从人类肠道病毒组中预测和识别候选Acrs.
- 开发一个结构相似性搜索功能,以识别基于3D结构的新Acrs.
主要方法:
- 利用AlphaFold2从肠道病毒组数据库预测候选Acrs的3D结构.
- 实现基于非序列相似性的工具 (TM-Vec,Foldseek,AcrPred) 用于与已知的Acrs进行结构比较.
- 执行了基于序列和结构的集群,以对已识别的Acr进行分类并分析关系.
主要成果:
- 更新的AcrDB包括795名候选Acrs的预测结构,其中121名候选人高度自信.
- 确定了44个候选Acr家族和119个已知的Acr家族之间的结构相似性.
- 发现,鉴定的Acrs的细菌宿主主要来自主导性肠道类 (Bacillota,Pseudomonadota,Bacteroidota).
结论:
- 增强的AcrDB为发现新型Anti-CRISPR蛋白质提供了宝贵的资源,特别是来自人类肠道微生物群.
- 结构相似性搜索有助于识别基于序列的方法遗漏的Acrs.
- 这些发现突显了肠道细菌群体内ACRS的流行率和潜在重要性,用于菌体防御和生物技术应用.
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