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Crystal structure of 2C helicase from enterovirus 71
Hongxin Guan1, Juan Tian1, Bo Qin1
1Ministry of Health Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 9 Dong Dan San Tiao, Beijing 100730, China.
Science Advances
|May 17, 2017
Summary
Enterovirus 71 nonstructural protein 2C is crucial for viral replication. Its unique self-oligomerization mechanism, revealed by crystal structure, offers a new target for antiviral drug development.
Area of Science:
- Virology
- Structural Biology
- Biochemistry
Background:
- Enterovirus 71 (EV71) causes hand, foot, and mouth disease outbreaks.
- EV71 nonstructural protein 2C's role in viral replication is not fully understood.
- Lack of high-resolution structure hindered understanding of 2C function and inhibitor design.
Purpose of the Study:
- To determine the high-resolution crystal structure of EV71 2C.
- To elucidate the mechanism of EV71 2C self-oligomerization and its relation to ATPase activity.
- To identify potential strategies for inhibiting enterovirus replication.
Main Methods:
- X-ray crystallography to obtain a 2.5 Å resolution structure of soluble EV71 2C.
- Biochemical assays to investigate 2C ATPase activity and self-oligomerization.
- Analysis of the structural basis for carboxyl terminus-mediated self-oligomerization.
Main Results:
- The crystal structure revealed EV71 2C possesses an ATPase domain, a zinc finger, and a helical domain.
- EV71 2C exhibits unique carboxyl terminus-mediated self-oligomerization, distinct from other AAA+ ATPases.
- This self-oligomerization is essential for 2C ATPase activity and EV71 replication.
Conclusions:
- The carboxyl terminus-mediated self-oligomerization interface of EV71 2C is critical for viral replication.
- Disrupting this self-oligomerization interface presents a promising strategy for developing novel antiviral therapies against enteroviruses.
Keywords:
2C ATPaseAAA+ superfamilyC-terminus mediated oligomerizationEV71Virus replicationZinc fingerantiviral drug designcrystal structureenteroviruspicornavirusMore Related Videos
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