Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell. 2017 Mar 23;169(1):47-57.e11. doi: 10.1016/j.cell.2017.03.012.

Structure Reveals Mechanisms of Viral Suppressors that Intercept a CRISPR RNA-Guided Surveillance Complex.

Author information

1
Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
2
Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59717, USA.
3
Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94158, USA.
4
Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
5
Department of Biochemistry, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
6
Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT 59840, USA.
7
Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: glander@scripps.edu.
8
Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59717, USA. Electronic address: bwiedenheft@gmail.com.

Abstract

Genetic conflict between viruses and their hosts drives evolution and genetic innovation. Prokaryotes evolved CRISPR-mediated adaptive immune systems for protection from viral infection, and viruses have evolved diverse anti-CRISPR (Acr) proteins that subvert these immune systems. The adaptive immune system in Pseudomonas aeruginosa (type I-F) relies on a 350 kDa CRISPR RNA (crRNA)-guided surveillance complex (Csy complex) to bind foreign DNA and recruit a trans-acting nuclease for target degradation. Here, we report the cryo-electron microscopy (cryo-EM) structure of the Csy complex bound to two different Acr proteins, AcrF1 and AcrF2, at an average resolution of 3.4 Å. The structure explains the molecular mechanism for immune system suppression, and structure-guided mutations show that the Acr proteins bind to residues essential for crRNA-mediated detection of DNA. Collectively, these data provide a snapshot of an ongoing molecular arms race between viral suppressors and the immune system they target.

KEYWORDS:

Acr; CRISPR; CRISPR-Cas; Cas; Csy; anti-CRISPRs; crRNA; cryo-EM; cryo-electron microscopy; type I-F

PMID:
28340349
PMCID:
PMC5478280
[Available on 2018-03-23]
DOI:
10.1016/j.cell.2017.03.012
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center