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TitleCas1 mediates the interference stage in a phage-encoded CRISPR-Cas system.
Journal, issue, pagesNat Chem Biol, Vol. 20, Issue 11, Page 1471-1481, Year 2024
Publish dateJul 8, 2024
AuthorsLaixing Zhang / Hao Wang / Jianwei Zeng / Xueli Cao / Zhengyu Gao / Zihe Liu / Feixue Li / Jiawei Wang / Yi Zhang / Maojun Yang / Yue Feng /
PubMed AbstractClustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems are prokaryotic adaptive immune systems against invading phages and other mobile genetic elements. Notably, some phages, ...Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems are prokaryotic adaptive immune systems against invading phages and other mobile genetic elements. Notably, some phages, including the Vibrio cholerae-infecting ICP1 (International Center for Diarrheal Disease Research, Bangladesh cholera phage 1), harbor CRISPR-Cas systems to counteract host defenses. Nevertheless, ICP1 Cas8f lacks the helical bundle domain essential for recruitment of helicase-nuclease Cas2/3 during target DNA cleavage and how this system accomplishes the interference stage remains unknown. Here, 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 CRISPR-associated complex for antiviral defense (Cascade; CRISPR system yersinia, Csy) of the ICP1 CRISPR-Cas system. A series of structures of Csy, Csy-dsDNA (double-stranded DNA), Cas1-Cas2/3 and Csy-dsDNA-Cas1-Cas2/3 complexes 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 the study also sheds light on a unique model of primed adaptation.
External linksNat Chem Biol / PubMed:38977786
MethodsEM (single particle) / X-ray diffraction
Resolution2.365 - 3.54 Å
Structure data

36831

8k28

EMDB-36831, PDB-8k28:
ICP1 Csy-dsDNA complex (form 1)
Method: EM (single particle) / Resolution: 3.54 Å

PDB-8k0h:
Structure of Cas5f-8f
Method: X-RAY DIFFRACTION / Resolution: 2.56 Å

PDB-8k0j:
Crystal structure of Cas7f
Method: X-RAY DIFFRACTION / Resolution: 2.365 Å

PDB-8k0k:
Crystal structure of Csy complex
Method: X-RAY DIFFRACTION / Resolution: 2.995 Å

Chemicals

ChemComp-HOH:
WATER

Source
  • vibrio phage icp1_2004_a (virus)
  • vibrio phage icp1_2011_a (virus)
KeywordsRNA BINDING PROTEIN / dimer / complex / DNA binding / RNA BINDING PROTEIN/RNA / RNA-protein complex / RNA BINDING PROTEIN-RNA complex / RNA BINDING PROTEIN/DNA/RNA / IMMUNE SYSTEM-RNA-DNA complex / RNA BINDING PROTEIN-DNA-RNA complex

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