小柯机器人

美国洛克菲勒大学Luciano A. Marraffini等研究人员合作发现，CRISPR效应物Cam1介导膜去极化来实现噬菌体防御。2024年1月10日，《自然》杂志在线发表了这项成果。

研究人员表示，原核生物III型CRISPR-Cas系统利用CRISPR相关罗斯曼折叠（CARF）蛋白效应器提供对病毒和质粒的免疫力。这些入侵者的转录本具有与CRISPR RNA向导互补的序列，识别这些转录本会产生环状寡腺苷酸第二信使，第二信使与CARF结构域结合并触发效应器结构域的活性。大多数效应物会降解宿主和入侵者的核酸，而有些效应物则含有跨膜螺旋，但没有酶的功能。这些CARF-跨膜螺旋融合蛋白是否以及如何促进III型CRISPR-Cas免疫反应仍然未知。

研究人员报道了环状寡腺苷酸激活膜蛋白1（Cam1）在III型CRISPR免疫中的作用。结构和生化分析表明，Cam1二聚体的CARF结构域与环四腺苷酸第二信使结合。在体内，Cam1定位于膜，预计会形成一个四聚体跨膜孔，并通过诱导膜去极化和生长停滞来抵御病毒感染。这些结果表明，CRISPR免疫并不总是通过降解核酸来发挥作用，而是通过更广泛的细胞反应来介导。

附：英文原文

Title: The CRISPR effector Cam1 mediates membrane depolarization for phage defence

Author: Baca, Christian F., Yu, You, Rostl, Jakob T., Majumder, Puja, Patel, Dinshaw J., Marraffini, Luciano A.

Issue&Volume: 2024-01-10

Abstract: Prokaryotic type III CRISPR–Cas systems provide immunity against viruses and plasmids using CRISPR-associated Rossman fold (CARF) protein effectors1,2,3,4,5. Recognition of transcripts of these invaders with sequences that are complementary to CRISPR RNA guides leads to the production of cyclic oligoadenylate second messengers, which bind CARF domains and trigger the activity of an effector domain6,7. Whereas most effectors degrade host and invader nucleic acids, some are predicted to contain transmembrane helices without an enzymatic function. Whether and how these CARF–transmembrane helix fusion proteins facilitate the type III CRISPR–Cas immune response remains unknown. Here we investigate the role of cyclic oligoadenylate-activated membrane protein 1 (Cam1) during type III CRISPR immunity. Structural and biochemical analyses reveal that the CARF domains of a Cam1 dimer bind cyclic tetra-adenylate second messengers. In vivo, Cam1 localizes to the membrane, is predicted to form a tetrameric transmembrane pore, and provides defence against viral infection through the induction of membrane depolarization and growth arrest. These results reveal that CRISPR immunity does not always operate through the degradation of nucleic acids, but is instead mediated via a wider range of cellular responses.

DOI: 10.1038/s41586-023-06902-y

Source: https://www.nature.com/articles/s41586-023-06902-y

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html