Abstract

African swine fever virus (ASFV) is highly contagious and can cause lethal disease in pigs. ASFV is primarily replicated in the cytoplasm of pig macrophages, which is oxidative and caused constant damage to ASFV genome. ASFV AP endonuclease (AsfvAP) catalyzes DNA cleavage reaction at the abasic site and is a key enzyme of ASFV base excision repair (BER) system. Although it plays an essential role in ASFV survival in host cells, the basis underlying substrate binding and cleavage by AsfvAP remains unclear. Here, we reported the structural and functional studies of AsfvAP, showing that AsfvAP adopts a novel DNA-binding mode distinct from other APs. AsfvAP possesses many unique structural features, including one narrower nucleotide-binding pocket at the active site, the C16–C20 disulfide bond-containing region, and histidine-rich loop. As indicated by our mutagenesis, in vitro binding and cleavage assays, these features are important for AsfvAP to suit the acidic and oxidative environment. Owing to their functional importance, these unique features could serve as targets for designing small molecule inhibitors that could disrupt the repair process of ASFV genome and help fight against this deadly virus in the future.

Details

Title
A unique DNA-binding mode of African swine fever virus AP endonuclease
Author
Chen, Yiqing 1 ; Chen, Xi 1 ; Huang, Qi 1 ; Shao Zhiwei 1 ; Gao Yanqing 1 ; Li, Yangyang 1 ; Yang, Chun 1 ; Liu Hehua 1 ; Li, Jixi 1   VIAFID ORCID Logo  ; Wang Qiyao 2 ; Ma Jinbiao 1   VIAFID ORCID Logo  ; Yong-Zhen, Zhang 3 ; Gu Yijun 4 ; Gan Jianhua 1 

1  Fudan University, State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Shanghai Public Health Clinical Center, School of Life Sciences, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443) 
2  East China University of Science and Technology, State Key Laboratory of Bioreactor Engineering, Shanghai, China (GRID:grid.28056.39) (ISNI:0000 0001 2163 4895) 
3  Fudan University, Shanghai Public Health Clinical Center, School of Life Sciences, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443); Chinese Center for Disease Control and Prevention, Changping, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Beijing, China (GRID:grid.198530.6) (ISNI:0000 0000 8803 2373) 
4  Chinese Academy of Sciences, National Center for Protein Science Shanghai, Shanghai Advanced Research Institute, Shanghai, China (GRID:grid.9227.e) (ISNI:0000000119573309) 
Publication year
2020
Publication date
2020
Publisher
Springer Nature B.V.
e-ISSN
20565968
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41421-020-0146-2
ProQuest document ID
2377674359
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.