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结构与机制分析揭示了米米病毒噬病毒体抗性元件系统中一种独特的类Cas4蛋白。

Structural and Mechanistic Analyses Reveal a Unique Cas4-like Protein in the Mimivirus Virophage Resistance Element System.

作者信息

Dou Chao, Yu Mingjing, Gu Yijun, Wang Jinjing, Yin Kun, Nie Chunlai, Zhu Xiaofeng, Qi Shiqian, Wei Yuquan, Cheng Wei

机构信息

Division of Respiratory and Critical Care Medicine, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University and Collaborative Innovation Center of Biotherapy, 17th, 3rd Section, Southern Renmin Road, Chengdu, 610041, China.

Shanghai Synchrotron Radiation Facility, Zhangjiang Lab, Zhangheng Road 239, Pudong District, Shanghai, 201203, China.

出版信息

iScience. 2018 May 25;3:1-10. doi: 10.1016/j.isci.2018.04.001. Epub 2018 Apr 11.

DOI:10.1016/j.isci.2018.04.001
PMID:30428313
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6137704/
Abstract

A clustered regularly interspaced short palindromic repeats (CRISPR)-like "mimivirus virophage resistance element" (MIMIVIRE) system, which contains specific cascade genes and a CRISPR array against virophages, was reported in mimiviruses. An essential component of the MIMIVIRE system is R354, encoding a nuclease and a likely functional homolog of Cas4. Here we show that R354 is a dual nuclease with both exonuclease and endonuclease activities. Structural analysis revealed that the catalytic core domain of R354 is similar to those of Cas4 and ? exonuclease despite their low sequence identity. R354 forms a homodimer that is important for its exonuclease but not endonuclease activity. Structural comparisons between the active and semi-active states of R354 demonstrated that an activation loop adjacent to the catalytic site is critical for enzymatic activity. Overall, the results suggest that R354 belongs to a novel MIMIVIRE system involved in innate virus immunity and provides a template for the identification of new CRISPR systems in other species.

摘要

在拟菌病毒中报道了一种成簇规律间隔短回文重复序列（CRISPR）样的“拟菌病毒噬病毒体抗性元件”（MIMIVIRE）系统，该系统包含特定的级联基因和一个针对噬病毒体的CRISPR阵列。MIMIVIRE系统的一个重要组成部分是R354，它编码一种核酸酶以及可能是Cas4的功能同源物。在此我们表明，R354是一种具有核酸外切酶和核酸内切酶活性的双功能核酸酶。结构分析显示，尽管R354与Cas4和δ核酸外切酶的序列同一性较低，但其催化核心结构域与它们相似。R354形成同源二聚体，这对其核酸外切酶活性而非核酸内切酶活性很重要。R354活性状态和半活性状态之间的结构比较表明，与催化位点相邻的激活环对酶活性至关重要。总体而言，结果表明R354属于一种参与先天性病毒免疫的新型MIMIVIRE系统，并为在其他物种中鉴定新的CRISPR系统提供了模板。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a652/6137704/435e7e676603/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a652/6137704/8be5d2762c22/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a652/6137704/d4bd2fcf424d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a652/6137704/3fda9f083f52/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a652/6137704/7f212903eb0d/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a652/6137704/6a35ca01b823/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a652/6137704/04f5f62ca336/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a652/6137704/b038a3f98b1a/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a652/6137704/435e7e676603/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a652/6137704/8be5d2762c22/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a652/6137704/d4bd2fcf424d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a652/6137704/3fda9f083f52/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a652/6137704/7f212903eb0d/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a652/6137704/6a35ca01b823/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a652/6137704/04f5f62ca336/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a652/6137704/b038a3f98b1a/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a652/6137704/435e7e676603/gr7.jpg

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2
Diversity, classification and evolution of CRISPR-Cas systems.CRISPR-Cas 系统的多样性、分类和进化。
Curr Opin Microbiol. 2017 Jun;37:67-78. doi: 10.1016/j.mib.2017.05.008. Epub 2017 Jun 9.
3
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4
Guarani Virophage, a New Sputnik-Like Isolate From a Brazilian Lake.瓜拉尼病毒噬菌体，一种从巴西湖泊中分离出的类似斯普特尼克的新型病毒。
Front Microbiol. 2019 May 3;10:1003. doi: 10.3389/fmicb.2019.01003. eCollection 2019.
5
Giant Viruses-Big Surprises.巨型病毒——巨大的惊喜。
Viruses. 2019 Apr 30;11(5):404. doi: 10.3390/v11050404.
6
Discovery and Further Studies on Giant Viruses at the IHU Mediterranee Infection That Modified the Perception of the Virosphere.在 IHU Mediterranee Infection 发现并进一步研究巨型病毒，改变了人们对病毒圈的认识。
Viruses. 2019 Mar 30;11(4):312. doi: 10.3390/v11040312.
7
Structure and mechanism of the Red recombination system of bacteriophage λ.噬菌体 λ 的 Red 重组系统的结构与机制。
Prog Biophys Mol Biol. 2019 Oct;147:33-46. doi: 10.1016/j.pbiomolbio.2019.03.005. Epub 2019 Mar 21.
8
Viva lavidaviruses! Five features of virophages that parasitize giant DNA viruses.噬病毒体万岁！寄生巨型DNA病毒的噬病毒体的五个特征。
PLoS Pathog. 2019 Mar 21;15(3):e1007592. doi: 10.1371/journal.ppat.1007592. eCollection 2019 Mar.
9
Ancestrality and Mosaicism of Giant Viruses Supporting the Definition of the Fourth TRUC of Microbes.巨型病毒的祖先特性与镶嵌性支持微生物第四域的定义
Front Microbiol. 2018 Nov 27;9:2668. doi: 10.3389/fmicb.2018.02668. eCollection 2018.
Nature. 2016 Mar 10;531(7593):249-52. doi: 10.1038/nature17146. Epub 2016 Feb 29.
4
An updated evolutionary classification of CRISPR-Cas systems.CRISPR-Cas系统的最新进化分类
Nat Rev Microbiol. 2015 Nov;13(11):722-36. doi: 10.1038/nrmicro3569. Epub 2015 Sep 28.
5
The CRISPR-associated Cas4 protein Pcal_0546 from Pyrobaculum calidifontis contains a [2Fe-2S] cluster: crystal structure and nuclease activity.来自嗜热栖热放线菌的CRISPR相关Cas4蛋白Pcal_0546含有一个[2Fe-2S]簇：晶体结构和核酸酶活性。
Nucleic Acids Res. 2014;42(17):11144-55. doi: 10.1093/nar/gku797. Epub 2014 Sep 8.
6
Zamilon, a novel virophage with Mimiviridae host specificity.扎米隆，一种对巨型病毒科宿主具有特异性的新型噬病毒体。
PLoS One. 2014 Apr 18;9(4):e94923. doi: 10.1371/journal.pone.0094923. eCollection 2014.
7
Toroidal structure and DNA cleavage by the CRISPR-associated [4Fe-4S] cluster containing Cas4 nuclease SSO0001 from Sulfolobus solfataricus.环型结构与 CRISPR 相关的 [4Fe-4S] 簇内 Cas4 核酸酶 SSO0001 对 DNA 的切割作用，来自于嗜热硫化叶菌（Sulfolobus solfataricus）。
J Am Chem Soc. 2013 Nov 20;135(46):17476-87. doi: 10.1021/ja408729b. Epub 2013 Nov 11.
8
CRISPR-mediated adaptive immune systems in bacteria and archaea.细菌和古菌中的 CRISPR 介导适应性免疫系统。
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