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• W2891617787 startingPage "e1007304" @default.
• W2891617787 abstract "Poliovirus (PV) 2CATPase is the most studied 2C protein in the Picornaviridae family. It is involved in RNA replication, encapsidation and uncoating and many inhibitors have been found that target PV 2CATPase. Despite numerous investigations to characterize its functions, a high-resolution structure of PV 2C has not yet been determined. We report here the crystal structure of a soluble fragment of PV 2CATPase to 2.55Å, containing an ATPase domain, a zinc finger and a C-terminal helical domain but missing the N-terminal domain. The ATPase domain shares the common structural features with EV71 2C and other Superfamily 3 helicases. The C-terminal cysteine-rich motif folds into a CCCC type zinc finger in which four cysteine ligands and several auxiliary residues assist in zinc binding. By comparing with the known zinc finger fold groups, we found the zinc finger of 2C proteins belong to a new fold group, which we denote the “Enterovirus 2C-like” group. The C-terminus of PV 2CATPase forms an amphipathic helix that occupies a hydrophobic pocket located on an adjacent PV 2CATPase in the crystal lattice. The C-terminus mediated PV 2C-2C interaction promotes self-oligomerization, most likely hexamerization, which is fundamental to the ATPase activity of 2C. The zinc finger is the most structurally diverse feature in 2C proteins. Available structural and virological data suggest that the zinc finger of 2C might confer the specificity of interaction with other proteins. We built a hexameric ring model of PV 2CATPase and visualized the previously identified functional motifs and drug-resistant sites, thus providing a structure framework for antiviral drug development." @default.
• W2891617787 created "2018-09-27" @default.
• W2891617787 creator A5000034150 @default.
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• W2891617787 date "2018-09-19" @default.
• W2891617787 modified "2023-10-10" @default.
• W2891617787 title "Crystal structure of a soluble fragment of poliovirus 2CATPase" @default.
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• W2891617787 doi "https://doi.org/10.1371/journal.ppat.1007304" @default.
• W2891617787 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6166989" @default.
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• W2891617787 hasPublicationYear "2018" @default.
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