7XT3

Crystal Structure of Hepatitis virus A 2C protein 128-335 aa

7XT3 の概要

• エントリーDOI: 10.2210/pdb7xt3/pdb
• 関連するPDBエントリー: 5GQ1 5GRB 5Z3Q
• 分子名称: Genome polyprotein, PHOSPHATE ION (3 entities in total)
• 機能のキーワード: viral protein, nonstructural protein 2c
• 由来する生物種: Hepatovirus A
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23798.89

構造登録者

Chen, P.,Wojdyla, J.A.,Li, Z.,Wang, M.,Cui, S. (登録日: 2022-05-16, 公開日: 2022-07-27, 最終更新日: 2024-05-29)

主引用文献

Chen, P.,Wojdyla, J.A.,Colasanti, O.,Li, Z.,Qin, B.,Wang, M.,Lohmann, V.,Cui, S.
Biochemical and structural characterization of hepatitis A virus 2C reveals an unusual ribonuclease activity on single-stranded RNA.
Nucleic Acids Res., 50:9470-9489, 2022

PubMed Abstract: The HAV nonstructural protein 2C is essential for virus replication; however, its precise function remains elusive. Although HAV 2C shares 24-27% sequence identity with other 2Cs, key motifs are conserved. Here, we demonstrate that HAV 2C is an ATPase but lacking helicase activity. We identified an ATPase-independent nuclease activity of HAV 2C with a preference for polyuridylic single-stranded RNAs. We determined the crystal structure of an HAV 2C fragment to 2.2 Å resolution, containing an ATPase domain, a region equivalent to enterovirus 2C zinc-finger (ZFER) and a C-terminal amphipathic helix (PBD). The PBD of HAV 2C occupies a hydrophobic pocket (Pocket) in the adjacent 2C, and we show the PBD-Pocket interaction is vital for 2C functions. We identified acidic residues that are essential for the ribonuclease activity and demonstrated mutations at these sites abrogate virus replication. We built a hexameric-ring model of HAV 2C, revealing the ribonuclease-essential residues clustering around the central pore of the ring, whereas the ATPase active sites line up at the gaps between adjacent 2Cs. Finally, we show the ribonuclease activity is shared by other picornavirus 2Cs. Our findings identified a previously unfound activity of picornavirus 2C, providing novel insights into the mechanisms of virus replication.

PubMed: 35947700
DOI: 10.1093/nar/gkac671

実験手法

X-RAY DIFFRACTION (2.15 Å)