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抗CRISPR病毒环核酸酶可破坏III型CRISPR免疫
2020-01-20 10:29

英国圣安德鲁斯大学Malcolm F. White、Tracey M. Gloster等研究人员合作发现,一种抗CRISPR病毒环核酸酶可破坏III型CRISPR免疫。2020年1月15日,国际知名学术期刊《自然》在线发表了这一成果。

研究人员确定了一个新的病毒抗CRISPR(Acr)酶家族,可以快速降解环状四腺苷酸(cA4)。病毒环核酸酶AcrIII-1广泛分布在古细菌和细菌病毒以及原病毒中。该酶使用以往未知的折叠特异性结合cA4,并使用保守的活性位点快速切割该信号分子,从而使病毒能够中和III型CRISPR防御系统。AcrIII-1家族具有广泛的宿主范围,因为它靶向cA4信号分子而不是特定的CRISPR效应蛋白。这项发现突出了环状核苷酸信号在病毒与其宿主之间冲突中的关键作用。

据了解,细菌和古细菌中的CRISPR系统提供针对移动遗传元件的适应性免疫力。III型CRISPR系统检测病毒RNA,从而激活Cas10蛋白的两个区域:一个HD核酸酶结构域(可降解病毒DNA)和一个环化酶结构域(可从ATP合成环状低聚腺苷酸)。环状低聚腺苷酸反过来会激活具有CRISPR关联的Rossmann折叠结构域的防御酶,激发出强大的抗病毒反应,从而将病毒驱赶灭绝。环状核苷酸越来越多地参与宿主与病原体的相互作用。

附:英文原文

Title: An anti-CRISPR viral ring nuclease subverts type III CRISPR immunity

Author: Januka S. Athukoralage, Stephen A. McMahon, Changyi Zhang, Sabine Grschow, Shirley Graham, Mart Krupovic, Rachel J. Whitaker, Tracey M. Gloster, Malcolm F. White

Issue&Volume: 2020-01-15

Abstract: The CRISPR system in bacteria and archaea provides adaptive immunity against mobile genetic elements. Type III CRISPR systems detect viral RNA, resulting in the activation of two regions of the Cas10 protein: an HD nuclease domain (which degrades viral DNA)1,2 and a cyclase domain (which synthesizes cyclic oligoadenylates from ATP)3,4,5. Cyclic oligoadenylates in turn activate defence enzymes with a CRISPR-associated Rossmann fold domain6, sculpting a powerful antiviral response7,8,9,10 that can drive viruses to extinction7,8. Cyclic nucleotides are increasingly implicated in host–pathogen interactions11,12,13. Here we identify a new family of viral anti-CRISPR (Acr) enzymes that rapidly degrade cyclic tetra-adenylate (cA4). The viral ring nuclease AcrIII-1 is widely distributed in archaeal and bacterial viruses and in proviruses. The enzyme uses a previously unknown fold to bind cA4 specifically, and a conserved active site to rapidly cleave this signalling molecule, allowing viruses to neutralize the type III CRISPR defence system. The AcrIII-1 family has a broad host range, as it targets cA4 signalling molecules rather than specific CRISPR effector proteins. Our findings highlight the crucial role of cyclic nucleotide signalling in the conflict between viruses and their hosts.

DOI: 10.1038/s41586-019-1909-5

Source: https://www.nature.com/articles/s41586-019-1909-5

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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