biostudies-literatureDolata KMEuropean Union11768https://www.ebi.ac.uk/biostudies/studies/S-EPMC12733259biostudies-literatureUnknown26(24)African swine fever virus (ASFV) causes a highly fatal disease in domestic pigs, resulting in substantial economic losses to the global swine industry. Vaccine development continues to be hindered by limited characterization of viral proteins and their functional redundancies. In this study, we employ combined experimental and computational approaches to characterize the ASFV I73R protein (pI73R), which contains a Z-DNA binding domain and plays a critical role in ASFV virulence and pathogenesis. We demonstrate that pI73R shares significant structural similarity with transcription factors of the forkhead box (FOX) protein family. Overexpression of pI73R results in downregulation of Crooked neck-like protein 1 (CRNKL1), a core spliceosome component, suggesting a potential mechanism by which International journal of molecular sciencesStructural and Functional Analysis of ASFV pI73R Reveals GNB1 Binding and Host Gene Modulation.PMC12733259862605Karger ADolata KMBettin BKuchler RPannhorst KFuchs WUshakov DSfalseStructural and Functional Analysis of ASFV pI73R Reveals GNB1 Binding and Host Gene Modulation.African swine fever virus (ASFV) causes a highly fatal disease in domestic pigs, resulting in substantial economic losses to the global swine industry. Vaccine development continues to be hindered by limited characterization of viral proteins and their functional redundancies. In this study, we employ combined experimental and computational approaches to characterize the ASFV I73R protein (pI73R), which contains a Z-DNA binding domain and plays a critical role in ASFV virulence and pathogenesis. We demonstrate that pI73R shares significant structural similarity with transcription factors of the forkhead box (FOX) protein family. Overexpression of pI73R results in downregulation of Crooked neck-like protein 1 (CRNKL1), a core spliceosome component, suggesting a potential mechanism by which 2025-01-01T00:00:00Z2025 Dec2026-05-28T03:24:22.661Z2026-05-28T03:12:16.736ZS-EPMC127332594146520010.3390/ijms262411768