Volume 27, No 7, Jul 2017
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 27 Issue 7, July 2017: 853-864
ORIGINAL ARTICLES
Alternate binding modes of anti-CRISPR viral suppressors AcrF1/2 to Csy surveillance complex revealed by cryo-EM structures
Ruchao Peng1,2,*, Ying Xu1,3,*, Tengfei Zhu2,4,*, Ningning Li5,*, Jianxun Qi1,2, Yan Chai1, Min Wu6, Xinzheng Zhang7, Yi Shi1,2,8,9, Peiyi Wang10, Jiawei Wang11, Ning Gao5 and George Fu Gao1,2,4,8,9,12
1CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
2University of Chinese Academy of Sciences, Beijing 101408, China
3School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China
4Research Network of Immunity and Health (RNIH), Beijing Institute of Life Science, Chinese Academy of Sciences, Beijing 100101, China
5State Key Laboratory of Membrane Biology, Peking-Tsinghua Center for Life Sciences, School of Life Sciences, Peking University, Beijing 100871, China
6Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA
7National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
8Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen, Guangdong 518112, China
9Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China
10Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
11State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China
12National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing 102206, China
Correspondence: George Fu Gao, Tel: 86-10-64807688 E-mail: gaof@im.ac.cn; Ning Gao, E-mail: gaon@pku.edu.cn; Jiawei Wang, E-mail: jwwang@tsinghua.edu.cn; Peiyi Wang,(fbspw@leeds.ac.uk)
Bacteriophages encode anti-CRISPR suppressors to counteract the CRISPR/Cas immunity of their bacterial hosts, thus facilitating their survival and replication. Previous studies have shown that two phage-encoded anti-CRISPR proteins, AcrF1 and AcrF2, suppress the type I-F CRISPR/Cas system of Pseudomonas aeruginosa by preventing target DNA recognition by the Csy surveillance complex, but the precise underlying mechanism was unknown. Here we present the structure of AcrF1/2 bound to the Csy complex determined by cryo-EM single-particle reconstruction. By structural analysis, we found that AcrF1 inhibits target DNA recognition of the Csy complex by interfering with base pairing between the DNA target strand and crRNA spacer. In addition, multiple copies of AcrF1 bind to the Csy complex with different modes when working individually or cooperating with AcrF2, which might exclude target DNA binding through different mechanisms. Together with previous reports, we provide a comprehensive working scenario for the two anti-CRISPR suppressors, AcrF1 and AcrF2, which silence CRISPR/Cas immunity by targeting the Csy surveillance complex.
10.1038/cr.2017.79
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