口蹄疫病毒
肽
病毒学
衣壳
病毒
生物
肽序列
口疮病毒
分子生物学
生物化学
基因
作者
Chu Zhang,Fan Yang,Justyna Aleksandra Wojdyla,Bo Qin,Wei Zhang,Min Zheng,Weijun Cao,Meitian Wang,Xiaopan Gao,Haixue Zheng,Sheng Cui
出处
期刊:Cell Reports
[Elsevier]
日期:2022-07-01
卷期号:40 (1): 111030-111030
被引量:4
标识
DOI:10.1016/j.celrep.2022.111030
摘要
The foot-and-mouth disease virus (FMDV) 2C protein shares conserved motifs with enterovirus 2Cs despite low sequence identity. Here, we determine the crystal structure of an FMDV 2C fragment to 1.83 Å resolution, which comprises an ATPase domain, a region equivalent to the enterovirus 2C zinc-finger (ZFER), and a C-terminal domain harboring a loop (PBL) that occupies a hydrophobic cleft (Pocket) in an adjacent 2C molecule. Mutations at ZFER, PBL, and Pocket affect FMDV 2C ATPase activity and are lethal to FMDV infectious clones. Because the PBL-Pocket interaction between FMDV 2C molecules is essential for its functions, we design an anti-FMDV peptide derived from PBL (PBL-peptide). PBL-peptide inhibits FMDV 2C ATPase activity, binds FMDV 2C with nanomolar affinity, and disrupts FMDV 2C oligomerization. FMDV 2C targets lipid droplets (LDs) and induces LD clustering in cells, and PBL-peptide disrupts FMDV 2C-induced LD clustering. Finally, we demonstrate that PBL-peptide exhibits anti-FMDV activity in cells.
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