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科学家发现一种环状核苷酸激活CRISPR蛋白酶的抗病毒信号传递
作者:小柯机器人 发布时间:2022/11/27 21:21:20

德国波恩大学Gregor Hagelueken等研究人员合作发现一种环状核苷酸激活CRISPR蛋白酶的抗病毒信号传递。这一研究成果于2022年11月24日在线发表在国际学术期刊《自然》上。

研究人员表示,CRISPR防御系统,如著名的DNA靶向Cas9和RNA靶向的III型系统,在原核生物中广泛存在。后者可以协调一个复杂的抗病毒反应,该反应是由外来RNA识别后合成的环状寡腺苷酸(cOA)启动的。在一大批与III型系统相关并被预测为与cOA结合的蛋白质中,一个与CRISPR相关的Lon蛋白酶(CalpL)让人们眼前一亮。该蛋白含有一个SAVED(SMODS相关并与各种效应域融合)家族的传感器域,与Lon蛋白酶效应域融合。然而,这种效应器的作用方式是未知的。

研究人员报告了CalpL的结构和功能,并表明该可溶性蛋白与另外两个蛋白CalpT和CalpS形成一个稳定的三方复合物,这两个蛋白在同一操纵子中编码。在被cA4激活后,CalpL寡聚并特异性地切割MazF同源物CalpT,从复合物中释放出细胞质外功能(ECF)Σ因子CalpS。这为基于CRISPR的外来核酸检测和转录调控之间提供了直接联系。此外,CRISPR效应器中存在一个cA4结合的SAVED结构域,这也揭示了与基于环状寡核苷酸的抗噬菌体信号系统(CBASS)的意外联系。

附:英文原文

Title: Antiviral signaling by a cyclic nucleotide activated CRISPR protease

Author: Rouillon, Christophe, Schneberger, Niels, Chi, Haotian, Blumenstock, Katja, Da Vela, Stefano, Ackermann, Katrin, Moecking, Jonas, Peter, Martin F., Boenigk, Wolfgang, Seifert, Reinhard, Bode, Bela E., Schmid-Burgk, Jonathan L., Svergun, Dmitri, Geyer, Matthias, White, Malcolm F., Hagelueken, Gregor

Issue&Volume: 2022-11-24

Abstract: CRISPR defense systems such as the well-known DNA-targeting Cas9 and the RNA-targeting type III systems are widespread in prokaryotes1,2. The latter can orchestrate a complex antiviral response that is initiated by the synthesis of cyclic oligoadenylates (cOAs) upon foreign RNA recognition3–5. Among a large set of proteins that were linked to type III systems and predicted to bind cOAs6,7, a CRISPR associated Lon protease (CalpL) stood out to us. The protein contains a sensor domain of the SAVED (SMODS-associated and fused to various effector domains) family7, fused to a Lon protease effector domain. However, the mode of action of this effector was unknown. Here, we report the structure and function of CalpL and show that the soluble protein forms a stable tripartite complex with two further proteins, CalpT and CalpS, that are encoded in the same operon. Upon activation by cA4, CalpL oligomerizes and specifically cleaves the MazF-homolog CalpT, releasing the extracytoplasmic function (ECF) sigma factor CalpS from the complex. This provides a direct connection between CRISPR-based foreign nucleic acid detection and transcriptional regulation. Furthermore, the presence of a cA4-binding SAVED domain in a CRISPR effector reveals an unexpected link to the cyclic oligonucleotide-based antiphage signaling system (CBASS).

DOI: 10.1038/s41586-022-05571-7

Source: https://www.nature.com/articles/s41586-022-05571-7

期刊信息

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