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PreprintCited by 12CRISPR and Genetic EngineeringBacteriophages and microbial interactionsBacterial Genetics and Biotechnology

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Cas1 mediates the interference stage in a phage-encoded CRISPR-Cas system

Open access
Zhang, Laixing, Wang, Hao, Zeng, Jianwei, Cao, Xueli, Gao, Zhengyu, Liu, Zihe, Li, Feixue, Wang, Jiawei, Zhang, Yi, Yang, Maojun, Feng, Yue·2024·Nature Chemical Biology
DOI 10.1101/2024.03.09.584257

Preprint — published as 10.1038/s41589-024-01659-5 · Paper page

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Abstract

CRISPR-Cas systems are prokaryotic adaptive immune systems against invading phages and other mobile genetic elements, which function in three stages: adaptation, expression and interference. Interestingly, phages were also found to encode CRISPR-Cas systems to antagonize their hosts and establish infection. The Vibrio cholerae -infecting ICP1 phage was the first discovered phage with a functional CRISPR-Cas system against an antiphage region in the host genome. Nevertheless, this system lacks a domain essential for recruitment of helicase-nuclease Cas2/3 during target DNA cleavage, and how this system accomplishes the interference stage remains unknown. Here, surprisingly, we found that Cas1, a highly conserved component known to exclusively work in the adaptation stage, also mediates the interference stage through connecting Cas2/3 to the DNA bound-Cascade (Csy) complex of the ICP1 CRISPR-Cas system. A series of structures of Csy, Csy-dsDNA, Cas1-Cas2/3 and Csy-dsDNA-Cas1-Cas2/3 complexes collectively reveal the whole process of Cas1-mediated target DNA cleavage by the ICP1 CRISPR-Cas system. Together, these data support an unprecedented model in which Cas1 mediates the interference stage in a phage-encoded CRISPR-Cas system and also shed light on a unique model of primed adaptation.

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Metadata

Authors
Zhang, L., Wang, H., Zeng, J., Cao, X., Gao, Z., Liu, Z., Li, F., Wang, J., Zhang, Y., Yang, M., & Feng, Y.
Affiliations
  • Center for Life Sciences (CN)
  • State Key Laboratory of Chemical Resource Engineering (CN)
  • Southern University of Science and Technology (CN)
Corresponding author
  • Zhang, Yi
  • Yang, Maojun
  • Feng, Yue
ORCID
Venue
Nature Chemical Biology
Publisher
openRxiv
Published
2024-03-11
Volume
20
Issue
11
Pages
1471-1481
ISSN
1552-4450 (ISSN-L)
DOI
10.1101/2024.03.09.584257
OpenAlex
W4400422905
Cited by
12
References
1
Citations by year
2026: 5 · 2025: 7
FWCI
1.63
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Nature Chemical Biology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Tsinghua University
  • Southern University of Science and Technology
  • National Key Research and Development Program of China
  • Institute of Microbiology, Chinese Academy of Sciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
CRISPR-Cas, Cas1, Vibrio cholerae, cascades, phage defense, adaptive immunity
MeSH terms
Bacteriophages, DNA, Vibrio cholerae, CRISPR-Cas Systems, CRISPR-Associated Proteins

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