The CRISPR-associated adenosine deaminase Cad1 converts ATP to ITP to provide antiviral immunity

IF 5.7 1区 化学 Q2 CHEMISTRY, PHYSICAL Journal of Chemical Theory and Computation Pub Date : 2024-10-28 DOI:10.1016/j.cell.2024.10.002
Christian F. Baca, Puja Majumder, James H. Hickling, Linzhi Ye, Marianna Teplova, Sean F. Brady, Dinshaw J. Patel, Luciano A. Marraffini
{"title":"The CRISPR-associated adenosine deaminase Cad1 converts ATP to ITP to provide antiviral immunity","authors":"Christian F. Baca, Puja Majumder, James H. Hickling, Linzhi Ye, Marianna Teplova, Sean F. Brady, Dinshaw J. Patel, Luciano A. Marraffini","doi":"10.1016/j.cell.2024.10.002","DOIUrl":null,"url":null,"abstract":"Type III CRISPR systems provide immunity against genetic invaders through the production of cyclic oligo-adenylate (cA<sub>n</sub>) molecules that activate effector proteins that contain CRISPR-associated Rossman fold (CARF) domains. Here, we characterized the function and structure of an effector in which the CARF domain is fused to an adenosine deaminase domain, CRISPR-associated adenosine deaminase 1 (Cad1). We show that upon binding of cA<sub>4</sub> or cA<sub>6</sub> to its CARF domain, Cad1 converts ATP to ITP, both <em>in vivo</em> and <em>in vitro</em>. Cryoelectron microscopy (cryo-EM) structural studies on full-length Cad1 reveal an hexameric assembly composed of a trimer of dimers, with bound ATP at inter-domain sites required for activity and ATP/ITP within deaminase active sites. Upon synthesis of cA<sub>n</sub> during phage infection, Cad1 activation leads to a growth arrest of the host that prevents viral propagation. Our findings reveal that CRISPR-Cas systems employ a wide range of molecular mechanisms beyond nucleic acid degradation to provide adaptive immunity in prokaryotes.","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":"109 1","pages":""},"PeriodicalIF":5.7000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Chemical Theory and Computation","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cell.2024.10.002","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0

Abstract

Type III CRISPR systems provide immunity against genetic invaders through the production of cyclic oligo-adenylate (cAn) molecules that activate effector proteins that contain CRISPR-associated Rossman fold (CARF) domains. Here, we characterized the function and structure of an effector in which the CARF domain is fused to an adenosine deaminase domain, CRISPR-associated adenosine deaminase 1 (Cad1). We show that upon binding of cA4 or cA6 to its CARF domain, Cad1 converts ATP to ITP, both in vivo and in vitro. Cryoelectron microscopy (cryo-EM) structural studies on full-length Cad1 reveal an hexameric assembly composed of a trimer of dimers, with bound ATP at inter-domain sites required for activity and ATP/ITP within deaminase active sites. Upon synthesis of cAn during phage infection, Cad1 activation leads to a growth arrest of the host that prevents viral propagation. Our findings reveal that CRISPR-Cas systems employ a wide range of molecular mechanisms beyond nucleic acid degradation to provide adaptive immunity in prokaryotes.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
CRISPR相关腺苷脱氨酶Cad1将ATP转化为ITP,提供抗病毒免疫力
III型CRISPR系统通过产生环状低聚腺苷酸(cAn)分子来激活含有CRISPR相关罗斯曼折叠(CARF)结构域的效应蛋白,从而提供抵御基因入侵者的免疫力。在这里,我们描述了一种效应蛋白的功能和结构,这种效应蛋白的CARF结构域与腺苷脱氨酶结构域融合,即CRISPR相关腺苷脱氨酶1(Cad1)。我们发现,当 cA4 或 cA6 与其 CARF 结构域结合后,Cad1 在体内和体外都能将 ATP 转化为 ITP。对全长 Cad1 的冷冻电子显微镜(cryo-EM)结构研究显示,Cad1 是由三聚体和二聚体组成的六聚体,结合的 ATP 位于活性所需的结构域间位点,ATP/ITP 位于脱氨酶活性位点。在噬菌体感染过程中合成 cAn 时,Cad1 激活会导致宿主生长停滞,从而阻止病毒传播。我们的研究结果表明,CRISPR-Cas系统在核酸降解之外还采用了多种分子机制,为原核生物提供适应性免疫。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Journal of Chemical Theory and Computation
Journal of Chemical Theory and Computation 化学-物理:原子、分子和化学物理
CiteScore
9.90
自引率
16.40%
发文量
568
审稿时长
1 months
期刊介绍: The Journal of Chemical Theory and Computation invites new and original contributions with the understanding that, if accepted, they will not be published elsewhere. Papers reporting new theories, methodology, and/or important applications in quantum electronic structure, molecular dynamics, and statistical mechanics are appropriate for submission to this Journal. Specific topics include advances in or applications of ab initio quantum mechanics, density functional theory, design and properties of new materials, surface science, Monte Carlo simulations, solvation models, QM/MM calculations, biomolecular structure prediction, and molecular dynamics in the broadest sense including gas-phase dynamics, ab initio dynamics, biomolecular dynamics, and protein folding. The Journal does not consider papers that are straightforward applications of known methods including DFT and molecular dynamics. The Journal favors submissions that include advances in theory or methodology with applications to compelling problems.
期刊最新文献
Linear Response pCCD-Based Methods: LR-pCCD and LR-pCCD+S Approaches for the Efficient and Reliable Modeling of Excited State Properties. Non-adiabatic Couplings in Surface Hopping with Tight Binding Density Functional Theory: The Case of Molecular Motors. Bayesian Approach for Computing Free Energy on Perturbation Graphs with Cycles. Deterministic and Faster GW Calculations with a Reduced Number of Valence States: O(N2 ln N) Scaling in the Plane-Waves Formalism. The Dynamic Diversity and Invariance of Ab Initio Water.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1