A cardioviral 2C-ATP complex structure reveals the essential role of a conserved arginine in regulation of cardioviral 2C activity.

ABSTRACT: 2C is a highly conserved picornaviral non-structural protein with ATPase activity and plays a multifunctional role in the viral life cycle as a promising target for anti-picornavirus drug development. While the structure-function of enteroviral 2Cs have been well studied, cardioviral 2Cs remain largely uncharacterized. Here, an endogenous ATP molecule was identified in the crystal structure of 2C from encephalomyocarditis virus (EMCV, Cardiovirus A). The ATP is bound into the ATPase active site with a unique compact conformation. Notably, the γ-phosphate of ATP directly interacts with Arg311 (conserved in cardioviral 2Cs), and its mutation significantly inhibits the ATPase activity. Unexpectedly, this mutation remarkably promotes 2C self-oligomerization and viral replication efficiency. Mo

SUBMITTER: He Q-Y 

PROVIDER: S-EPMC11495053 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature