7E6V

The crystal structure of foot-and-mouth disease virus(FMDV) 2C protein 97-318aa

Summary for 7E6V

• Entry DOI: 10.2210/pdb7e6v/pdb
• Descriptor: Protein 2C, ACETATE ION (3 entities in total)
• Functional Keywords: fmdv, 2c, hydrolase
• Biological source: Foot-and-mouth disease virus - type SAT 2
• Total number of polymer chains: 2
• Total formula weight: 50705.34

Authors

Zhang, C.,Wojdyla, J.A.,Qin, B.,Wang, M.,Gao, X.,Cui, S. (deposition date: 2021-02-24, release date: 2022-06-29, Last modification date: 2022-07-20)

Primary citation

Zhang, C.,Yang, F.,Wojdyla, J.A.,Qin, B.,Zhang, W.,Zheng, M.,Cao, W.,Wang, M.,Gao, X.,Zheng, H.,Cui, S.
An anti-picornaviral strategy based on the crystal structure of foot-and-mouth disease virus 2C protein.
Cell Rep, 40:111030-111030, 2022

PubMed Abstract: 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.

PubMed: 35793627
DOI: 10.1016/j.celrep.2022.111030

Experimental method

X-RAY DIFFRACTION (1.832 Å)