The research on the genetic mechanism of African swine fever virus (ASFV) DNA ligase (AsfvDNAL) was revealed by the research group of Gan Jianhua and the research team of Li Jixi, School of Life Sciences, Fudan University. The results were recently published online in Nature-Communication.

ASFV is a unique double-stranded DNA virus that causes death in infected pigs and has received widespread attention from researchers. Although it has been studied for more than 100 years, no effective vaccine has been reported. ASFV is a huge threat to pig farming in many countries and regions around the world, and it broke out in China for the first time in 2018, causing serious economic losses.

There is a complete DNA repair pathway in ASFV. Unlike the usual DNA repair pathways, the polymerase and ligase in the DNA repair pathway of ASFV are very low fidelity and play a key role in the repair and mutation of the ASFV genome.

It is reported that the team's previous research found that AsfvPolX has a unique phosphate recognition site, which is critical for its substrate binding and catalytic activity. "AsfvDNAL has low sequence similarity with homologous proteins, but the molecular mechanism of its tolerance for base mismatch is still unclear." The first author of the paper, Chen Yu, told the Journal of Chinese Academy of Sciences that researchers used X-ray crystallography. The high resolution structure of AsfvDNAL and different types of DNA complexes was successfully resolved.

The crystal structure shows that AsfvDNAL has a unique DNA binding domain that is important for substrate binding. Although AsfvDNAL is conserved in the catalytic mechanism with common DNA ligases, AsfvDNAL has some distinct amino acid compositions near the substrate catalytic site.

"Protein mutations, in vitro DNA binding, and activity studies have shown that amino acids near the catalytic site are critical for the formation and activity of catalytic forms of AsfvDNAL-DNA complexes." Gan Jianhua said the study was aimed at African swine fever virus DNA. The drug design of repairing pathway proteins provides a structural basis. (Reporter Huang Xin)

Source: Chinese Journal of Science

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