Crystal structure of 2C helicase from enterovirus 71
| العنوان: | Crystal structure of 2C helicase from enterovirus 71 |
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| المؤلفون: | Zhendong Zhao, Juan Tian, Bei Wang, Sheng Cui, Hongxin Guan, Bo Qin, Justyna Aleksandra Wojdyla, Meitian Wang |
| المصدر: | Science Advances |
| بيانات النشر: | American Association for the Advancement of Science (AAAS), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Protein Folding, crystal structure, Virus replication, Picornavirus, ATPase, 030106 microbiology, Crystallography, X-Ray, Viral Proteins, 03 medical and health sciences, Protein Domains, Viral life cycle, Structural Biology, Zinc finger, Hydrolase, Enterovirus 71, Protein Structure, Quaternary, Pathogen, Research Articles, Multidisciplinary, biology, enterovirus, EV71, SciAdv r-articles, Zinc Fingers, 2C ATPase, biology.organism_classification, Enterovirus A, Human, Cell biology, picornavirus, 030104 developmental biology, Biochemistry, Viral replication, biology.protein, antiviral drug design, Protein Multimerization, C-terminus mediated oligomerization, AAA+ superfamily, RNA Helicases, Research Article |
| الوصف: | Structure of EV71 2C unveils the structural basis of the functional mechanism of carboxyl terminus–mediated self-oligomerization. Enterovirus 71 (EV71) is the major pathogen responsible for outbreaks of hand, foot, and mouth disease. EV71 nonstructural protein 2C participates in many critical events throughout the virus life cycle; however, its precise role is not fully understood. Lack of a high-resolution structure made it difficult to elucidate 2C activity and prevented inhibitor development. We report the 2.5 Å–resolution crystal structure of the soluble part of EV71 2C, containing an adenosine triphosphatase (ATPase) domain, a cysteine-rich zinc finger with an unusual fold, and a carboxyl-terminal helical domain. Unlike other AAA+ ATPases, EV71 2C undergoes a carboxyl terminus–mediated self-oligomerization, which is dependent on a specific interaction between the carboxyl-terminal helix of one monomer and a deep pocket formed between the ATPase and the zinc finger domains of the neighboring monomer. The carboxyl terminus–mediated self-oligomerization is fundamental to 2C ATPase activity and EV71 replication. Our findings suggest a strategy for inhibition of enterovirus replication by disruption of the self-oligomerization interface of 2C. |
| تدمد: | 2375-2548 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3e47e5d12ba847c79618aa4a1adae38aTest https://doi.org/10.1126/sciadv.1602573Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3e47e5d12ba847c79618aa4a1adae38a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23752548 |
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