TY - JOUR
T1 - Cas1 mediates the interference stage in a phage-encoded CRISPR–Cas system
AU - Zhang, Laixing
AU - Wang, Hao
AU - Zeng, Jianwei
AU - Cao, Xueli
AU - Gao, Zhengyu
AU - Liu, Zihe
AU - Li, Feixue
AU - Wang, Jiawei
AU - Zhang, Yi
AU - Yang, Maojun
AU - Feng, Yue
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.
PY - 2024/11
Y1 - 2024/11
N2 - 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. (Figure presented.)
AB - 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. (Figure presented.)
UR - http://www.scopus.com/inward/record.url?scp=85197772232&partnerID=8YFLogxK
U2 - 10.1038/s41589-024-01659-5
DO - 10.1038/s41589-024-01659-5
M3 - Article
C2 - 38977786
AN - SCOPUS:85197772232
SN - 1552-4450
VL - 20
SP - 1471
EP - 1481
JO - Nature Chemical Biology
JF - Nature Chemical Biology
IS - 11
ER -