IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-34551-8.html
   My bibliography  Save this article

A redox switch regulates the assembly and anti-CRISPR activity of AcrIIC1

Author

Listed:
  • Yanan Zhao

    (Harbin Institute of Technology)

  • Jiaojiao Hu

    (Chinese Academy of Sciences)

  • Shan-Shan Yang

    (School of Environment, Harbin Institute of Technology)

  • Jing Zhong

    (Harbin Institute of Technology)

  • Jianping Liu

    (Chinese Academy of Sciences)

  • Shuo Wang

    (Harbin Institute of Technology)

  • Yuzhuo Jiao

    (Harbin Institute of Technology)

  • Fang Jiang

    (Harbin Institute of Technology)

  • Ruiyang Zhai

    (Harbin Institute of Technology)

  • Bingnan Ren

    (Harbin Institute of Technology)

  • Hua Cong

    (Harbin Institute of Technology)

  • Yuwei Zhu

    (Harbin Institute of Technology)

  • Fengtong Han

    (Harbin Institute of Technology)

  • Jixian Zhang

    (Harbin Institute of Technology)

  • Yue Xu

    (Harbin Institute of Technology)

  • Zhiwei Huang

    (Harbin Institute of Technology)

  • Shengnan Zhang

    (Chinese Academy of Sciences)

  • Fan Yang

    (Harbin Institute of Technology)

Abstract

Anti-CRISPRs (Acrs) are natural inhibitors of bacteria’s CRISPR-Cas systems, and have been developed as a safeguard to reduce the off-target effects of CRISPR gene-editing technology. Acrs can directly bind to CRISPR-Cas complexes and inhibit their activities. However, whether this process is under regulation in diverse eukaryotic cellular environments is poorly understood. In this work, we report the discovery of a redox switch for NmeAcrIIC1, which regulates NmeAcrIIC1’s monomer-dimer interconversion and inhibitory activity on Cas9. Further structural studies reveal that a pair of conserved cysteines mediates the formation of inactive NmeAcrIIC1 dimer and directs the redox cycle. The redox switch also applies to the other two AcrIIC1 orthologs. Moreover, by replacing the redox-sensitive cysteines, we generated a robust AcrIIC1 variant that maintains potent inhibitory activity under various redox conditions. Our results reveal a redox-dependent regulation mechanism of Acr, and shed light on the design of superior Acr for CRISPR-Cas systems.

Suggested Citation

  • Yanan Zhao & Jiaojiao Hu & Shan-Shan Yang & Jing Zhong & Jianping Liu & Shuo Wang & Yuzhuo Jiao & Fang Jiang & Ruiyang Zhai & Bingnan Ren & Hua Cong & Yuwei Zhu & Fengtong Han & Jixian Zhang & Yue Xu , 2022. "A redox switch regulates the assembly and anti-CRISPR activity of AcrIIC1," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34551-8
    DOI: 10.1038/s41467-022-34551-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-34551-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-34551-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. De Dong & Minghui Guo & Sihan Wang & Yuwei Zhu & Shuo Wang & Zhi Xiong & Jianzheng Yang & Zengliang Xu & Zhiwei Huang, 2017. "Structural basis of CRISPR–SpyCas9 inhibition by an anti-CRISPR protein," Nature, Nature, vol. 546(7658), pages 436-439, June.
    2. Muneaki Nakamura & Prashanth Srinivasan & Michael Chavez & Matthew A. Carter & Antonia A. Dominguez & Marie La Russa & Matthew B. Lau & Timothy R. Abbott & Xiaoshu Xu & Dehua Zhao & Yuchen Gao & Natha, 2019. "Anti-CRISPR-mediated control of gene editing and synthetic circuits in eukaryotic cells," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    3. Joseph Bondy-Denomy & Bianca Garcia & Scott Strum & Mingjian Du & MaryClare F. Rollins & Yurima Hidalgo-Reyes & Blake Wiedenheft & Karen L. Maxwell & Alan R. Davidson, 2015. "Multiple mechanisms for CRISPR–Cas inhibition by anti-CRISPR proteins," Nature, Nature, vol. 526(7571), pages 136-139, October.
    4. Joe Bondy-Denomy & April Pawluk & Karen L. Maxwell & Alan R. Davidson, 2013. "Bacteriophage genes that inactivate the CRISPR/Cas bacterial immune system," Nature, Nature, vol. 493(7432), pages 429-432, January.
    5. Beverly Y. Mok & Marcos H. de Moraes & Jun Zeng & Dustin E. Bosch & Anna V. Kotrys & Aditya Raguram & FoSheng Hsu & Matthew C. Radey & S. Brook Peterson & Vamsi K. Mootha & Joseph D. Mougous & David R, 2020. "A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing," Nature, Nature, vol. 583(7817), pages 631-637, July.
    6. Xiaoxue Wang & Younghoon Kim & Qun Ma & Seok Hoon Hong & Karina Pokusaeva & Joseph M. Sturino & Thomas K. Wood, 2010. "Cryptic prophages help bacteria cope with adverse environments," Nature Communications, Nature, vol. 1(1), pages 1-9, December.
    7. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    8. Annoj Thavalingam & Zhi Cheng & Bianca Garcia & Xue Huang & Megha Shah & Wei Sun & Min Wang & Lucas Harrington & Sungwon Hwang & Yurima Hidalgo-Reyes & Erik J. Sontheimer & Jennifer Doudna & Alan R. D, 2019. "Inhibition of CRISPR-Cas9 ribonucleoprotein complex assembly by anti-CRISPR AcrIIC2," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Xieshuting Deng & Wei Sun & Xueyan Li & Jiuyu Wang & Zhi Cheng & Gang Sheng & Yanli Wang, 2024. "An anti-CRISPR that represses its own transcription while blocking Cas9-target DNA binding," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Yi Yi & Shunzhang Liu & Yali Hao & Qingyang Sun & Xinjuan Lei & Yecheng Wang & Jiahua Wang & Mujie Zhang & Shan Tang & Qingxue Tang & Yue Zhang & Xipeng Liu & Yinzhao Wang & Xiang Xiao & Huahua Jian, 2023. "A systematic analysis of marine lysogens and proviruses," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Ning Duan & Emily Hand & Mannuku Pheko & Shikha Sharma & Akintunde Emiola, 2024. "Structure-guided discovery of anti-CRISPR and anti-phage defense proteins," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    4. Haifeng Sun & Zhaojun Wang & Limini Shen & Yeling Feng & Lu Han & Xuezhen Qian & Runde Meng & Kangming Ji & Dong Liang & Fei Zhou & Xin Lou & Jun Zhang & Bin Shen, 2023. "Developing mitochondrial base editors with diverse context compatibility and high fidelity via saturated spacer library," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Ye Yuan & Lei Chen & Kexu Song & Miaomiao Cheng & Ling Fang & Lingfei Kong & Lanlan Yu & Ruonan Wang & Zhendong Fu & Minmin Sun & Qian Wang & Chengjun Cui & Haojue Wang & Jiuyang He & Xiaonan Wang & Y, 2024. "Stable peptide-assembled nanozyme mimicking dual antifungal actions," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    6. Ivica Odorčić & Mohamed Belal Hamed & Sam Lismont & Lucía Chávez-Gutiérrez & Rouslan G. Efremov, 2024. "Apo and Aβ46-bound γ-secretase structures provide insights into amyloid-β processing by the APH-1B isoform," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    7. Léon Faure & Bastien Mollet & Wolfram Liebermeister & Jean-Loup Faulon, 2023. "A neural-mechanistic hybrid approach improving the predictive power of genome-scale metabolic models," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    8. Tian Zhu & Merry H. Ma, 2022. "Deriving the Optimal Strategy for the Two Dice Pig Game via Reinforcement Learning," Stats, MDPI, vol. 5(3), pages 1-14, August.
    9. Stella Vitt & Simone Prinz & Martin Eisinger & Ulrich Ermler & Wolfgang Buckel, 2022. "Purification and structural characterization of the Na+-translocating ferredoxin: NAD+ reductase (Rnf) complex of Clostridium tetanomorphum," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    10. Pierre Azoulay & Joshua Krieger & Abhishek Nagaraj, 2024. "Old Moats for New Models: Openness, Control, and Competition in Generative AI," NBER Chapters, in: Entrepreneurship and Innovation Policy and the Economy, volume 4, National Bureau of Economic Research, Inc.
    11. Riya Shah & Thomas C. Panagiotou & Gregory B. Cole & Trevor F. Moraes & Brigitte D. Lavoie & Christopher A. McCulloch & Andrew Wilde, 2024. "The DIAPH3 linker specifies a β-actin network that maintains RhoA and Myosin-II at the cytokinetic furrow," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    12. Yashan Yang & Qianqian Shao & Mingcheng Guo & Lin Han & Xinyue Zhao & Aohan Wang & Xiangyun Li & Bo Wang & Ji-An Pan & Zhenguo Chen & Andrei Fokine & Lei Sun & Qianglin Fang, 2024. "Capsid structure of bacteriophage ΦKZ provides insights into assembly and stabilization of jumbo phages," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    13. Anthony C. Bishop & Glorisé Torres-Montalvo & Sravya Kotaru & Kyle Mimun & A. Joshua Wand, 2023. "Robust automated backbone triple resonance NMR assignments of proteins using Bayesian-based simulated annealing," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    14. Bret M. Boyd & Ian James & Kevin P. Johnson & Robert B. Weiss & Sarah E. Bush & Dale H. Clayton & Colin Dale, 2024. "Stochasticity, determinism, and contingency shape genome evolution of endosymbiotic bacteria," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    15. Jun-Yu Si & Yuan-Mei Chen & Ye-Hui Sun & Meng-Xue Gu & Mei-Ling Huang & Lu-Lu Shi & Xiao Yu & Xiao Yang & Qing Xiong & Cheng-Bao Ma & Peng Liu & Zheng-Li Shi & Huan Yan, 2024. "Sarbecovirus RBD indels and specific residues dictating multi-species ACE2 adaptiveness," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    16. Deyun Qiu & Jinxin V. Pei & James E. O. Rosling & Vandana Thathy & Dongdi Li & Yi Xue & John D. Tanner & Jocelyn Sietsma Penington & Yi Tong Vincent Aw & Jessica Yi Han Aw & Guoyue Xu & Abhai K. Tripa, 2022. "A G358S mutation in the Plasmodium falciparum Na+ pump PfATP4 confers clinically-relevant resistance to cipargamin," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    17. Shuo-Shuo Liu & Tian-Xia Jiang & Fan Bu & Ji-Lan Zhao & Guang-Fei Wang & Guo-Heng Yang & Jie-Yan Kong & Yun-Fan Qie & Pei Wen & Li-Bin Fan & Ning-Ning Li & Ning Gao & Xiao-Bo Qiu, 2024. "Molecular mechanisms underlying the BIRC6-mediated regulation of apoptosis and autophagy," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    18. Dick Schijven & Sourena Soheili-Nezhad & Simon E. Fisher & Clyde Francks, 2024. "Exome-wide analysis implicates rare protein-altering variants in human handedness," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    19. Ahrum Son & Hyunsoo Kim & Jolene K. Diedrich & Casimir Bamberger & Daniel B. McClatchy & Stuart A. Lipton & John R. Yates, 2024. "Using in vivo intact structure for system-wide quantitative analysis of changes in proteins," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    20. Justin N. Vaughn & Sandra E. Branham & Brian Abernathy & Amanda M. Hulse-Kemp & Adam R. Rivers & Amnon Levi & William P. Wechter, 2022. "Graph-based pangenomics maximizes genotyping density and reveals structural impacts on fungal resistance in melon," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34551-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.