| Anti-CRISPR蛋白AcrVA2的结构生物学研究 |
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| 引用本文： | 陈鹏,孙伟,程志,杨晶,王敏,王久宇,陈慧卿,刘亮,王艳丽.Anti-CRISPR蛋白AcrVA2的结构生物学研究[J].生物化学与生物物理进展,2021,48(1):77-87. |
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| 作者姓名： | 陈鹏 孙伟 程志 杨晶 王敏 王久宇 陈慧卿 刘亮 王艳丽 |
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| 作者单位： | 3）中国科学院生物物理研究所，生物大分子国家实验室，北京 100101,3）中国科学院生物物理研究所，生物大分子国家实验室，北京 100101,3）中国科学院生物物理研究所，生物大分子国家实验室，北京 100101,1）中国科学院生物物理研究所，中国科学院生物大分子卓越中心，核酸重点实验室，北京 100101,1）中国科学院生物物理研究所，中国科学院生物大分子卓越中心，核酸重点实验室，北京 100101,3）中国科学院生物物理研究所，生物大分子国家实验室，北京 100101,4）江苏大学生命科学学院，镇江 212000,5）厦门大学生命科学学院，厦门 361102,1）中国科学院生物物理研究所，中国科学院生物大分子卓越中心，核酸重点实验室，北京 100101 |
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| 基金项目： | 国家自然科学基金 (31930065, 31725008, 31630015, 31571335, 31700662, 91440201) 资助项目. |
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| 摘 要： | 大多数古生菌及半数细菌都含有成簇有规律间隔的短回文重复序列(clustered regularly interspaced short palindromic repeats,CRISPR)和CRISPR相关(CRISPR-associated,Cas)蛋白质构成的适应性免疫系统,来抵御外界噬菌体的入侵.而噬菌体为了对抗这种免疫系统,也进化出许多抗CRISPR(anti-CRISPR,Acr)的蛋白质,使得CRISPR-Cas系统受到抑制.来自牛眼莫拉氏菌(Moraxella bovoculi)的AcrVA2是目前发现的可抑制V-A型CRISPR-Cas系统效应蛋白Cas12a发挥切割活性的Acr蛋白之一,其作用机理尚不清楚.本文解析了自由状态的AcrVA2和MbCas12a620-636-AcrVA2复合物的晶体结构,发现AcrVA2蛋白采用了一种新的α-β折叠结构,且只与自由状态的Cas12a结合.此外,AcrVA2与MbCas12a620-636的结合主要依靠氢键和盐桥的相互作用力,并通过疏水界面得到进一步稳定.这些结果提示,AcrVA2是通过与自由状态的MbCas12a结合来发挥抑制活性的,这对进一步理解Acr蛋白抑制V-A型CRISPR-Cas系统的多样化机制有重要意义.
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| 关 键 词： | CRISPR-Cas系统 Cas12a Anti-CRISPR蛋白 AcrVA2 晶体结构 |
| 收稿时间： | 2020/7/7 0:00:00 |
| 修稿时间： | 2020/7/17 0:00:00 |
Structural Study on Anti-CRISPR Protein AcrVA2 |
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| CHEN Peng,SUN Wei,CHENG Zhi,YANG Jing,WANG Min,WANG Jiu-Yu,CHEN Hui-Qing,LIU Liang and WANG Yan-Li.Structural Study on Anti-CRISPR Protein AcrVA2[J].Progress In Biochemistry and Biophysics,2021,48(1):77-87. |
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| Authors: | CHEN Peng SUN Wei CHENG Zhi YANG Jing WANG Min WANG Jiu-Yu CHEN Hui-Qing LIU Liang and WANG Yan-Li |
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| Institution: | 3)National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China,3)National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China,3)National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China,1)Key Laboratory of RNA Biology, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics,Chinese Academy of Sciences, Beijing 100101, China,1)Key Laboratory of RNA Biology, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics,Chinese Academy of Sciences, Beijing 100101, China,3)National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China,4)School of Life Sciences, Jiangsu University, Zhenjiang 212000, China,5)School of Life Sciences, Xiamen University, Xiamen 361102, China,1)Key Laboratory of RNA Biology, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics,Chinese Academy of Sciences, Beijing 100101, China |
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| Abstract: | To defend against the invasion of phages,most Archaea and bacteria possess the adaptive immune systems,which are formed by clustered regularly interspaced short palindromic repeats(CRISPR)and CRISPR-associated(Cas)proteins.To counteract the CRISPR-Cas systems,phages express anti-CRISPR(Acr)proteins to inhibit CRISPR-dependent response.AcrVA2 from Moraxella bovoculi is an inhibitor of Type V-A CRISPR-Cas system.However,the structure and inhibition mechanism of AcrVA2 remain to be elucidated.Here we report the crystal structures of AcrVA2 in the apo state and MbCas12a620-636-AcrVA2 complex.AcrVA2 adopts a novelα-βfold and binds to MbCas12a in free state.The structure of MbCas12a620-636-AcrVA2 complex reveals that AcrVA2 interacts with MbCas12a via hydrogen bonds and salt bridges,as well as hydrophobic interaction.These results suggest that AcrVA2 affect the activity of Cas12a by binding to the MbCas12a in the apo state.These results provide significant insights into the mechanism of AcrVA2 disabling Type V-A CRISPR-Cas system. |
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| Keywords: | CRISPR-Cas system Cas12a anti-CRISPR AcrVA2 crystal structure |
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