Related Experiment Video
Updated: May 8, 2026

Multi-target Parallel Processing Approach for Gene-to-structure Determination of the Influenza Polymerase PB2 Subunit
Published on: June 28, 2013
Crystal structure of 2A proteinase from hand, foot and mouth disease virus
Zhixia Mu1, Bei Wang, Xiaoyu Zhang
1MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 9 Dong Dan San Tiao, Beijing 100730, People's Republic of China.
Abstract:
EV71 is responsible for several epidemics worldwide; however, the effective antiviral drug is unavailable to date. The 2A proteinase (2A(pro)) of EV71 presents a promising drug target due to its multiple roles in virus replication, inhibition of host protein synthesis and evasion of innate immunity. We determined the crystal structure of EV71 2A(pro) at 1.85Å resolution, revealing that the proteinase maintains a chymotrypsin-like fold. The active site is composed of the catalytic triads C110A, H21 and D39 with the geometry similar to that in other picornaviral 2A(pro), 3C(pro) and serine proteinases. The cI-to-eI2 loop at the N-terminal domain of EV71 2A(pro) adopts a highly stable conformation and contributes to the hydrophilic surface property, which are strikingly different in HRV2 2A(pro) but are similar in CVB4 2A(pro). We identified a hydrophobic motif "LLWL" followed by an acidic motif "DEE" at the C-terminus of EV71 2A(pro). The "LLWL" motif is folded into the β-turn structure that is essential for the positioning of the acidic motif. Our structural and mutagenesis study demonstrated that both the negative charging and the correct positioning of the C-terminus are essential for EV71 replication. Deletion of the "LLWL" motif abrogated the proteolytic activity, indicating that the motif is critical for maintaining the active proteinase conformation. Our findings provide the structural and functional insights into EV71 2A(pro) and establish a framework for structure-based inhibitor design.
Related Concept Videos
ATP Synthase: Structure
Protein Complex Assembly
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Leaky Scanning
Protein Organization
The primary structure of a protein is its amino acid sequence.
Protein and Protein Structure
A protein's shape is critical to its function. For example, an enzyme can...

