研究人员描述了一类依赖于环状寡腺苷酸（cAn）的效应蛋白，它们被命名为CRISPR-Cas相关信使RNA（mRNA）干扰素1（Cami1），由CRISPR相关Rossmann折叠传感器结构域融合翼螺旋-转螺旋和RelE家族mRNA干扰素结构域组成。被环状四腺苷酸（cA4）激活后，Cami1会切割暴露在核糖体A位点的mRNA，从而耗尽mRNA并导致细胞生长停滞。apo-Cami1和与核糖体结合的Cami1-cA4复合物的结构描述了导致Cami1激活的构象变化以及Cami1与细菌核糖体结合的机制，并揭示了与真核生物核糖体失活蛋白意想不到的相似之处。
据介绍，原核生物III型CRISPR-Cas抗病毒系统利用cAn信号来激活各种辅助蛋白，从而加强CRISPR-Cas的防御能力。
附：英文原文
Title: Ribosomal stalk-captured CARF-RelE ribonuclease inhibits translation following CRISPR signaling
Author: Irmantas Mogila, Giedre Tamulaitiene, Konstanty Keda, Albertas Timinskas, Audrone Ruksenaite, Giedrius Sasnauskas, eslovas Venclovas, Virginijus Siksnys, Gintautas Tamulaitis
Issue&Volume: 2023-12-01
Abstract: Prokaryotic type III CRISPR-Cas antiviral systems employ cyclic oligoadenylate (cAn) signaling to activate a diverse range of auxiliary proteins that reinforce the CRISPR-Cas defense. Here we characterize a class of cAn-dependent effector proteins named CRISPR-Cas-associated messenger RNA (mRNA) interferase 1 (Cami1) consisting of a CRISPR-associated Rossmann fold sensor domain fused to winged helix-turn-helix and a RelE-family mRNA interferase domain. Upon activation by cyclic tetra-adenylate (cA4), Cami1 cleaves mRNA exposed at the ribosomal A-site thereby depleting mRNA and leading to cell growth arrest. The structures of apo-Cami1 and the ribosome-bound Cami1-cA4 complex delineate the conformational changes that lead to Cami1 activation and the mechanism of Cami1 binding to a bacterial ribosome, revealing unexpected parallels with eukaryotic ribosome-inactivating proteins.
DOI: adj2107
Source: https://www.science.org/doi/10.1126/science.adj2107