Crystal structure of 2C helicase from enterovirus 71

Guan, Hongxin; Tian, Juan; Qin, Bo; Wojdyla, Justyna Aleksandra; Wang, Bei; Zhao, Zhendong; Wang, Meitian; Cui, Sheng

doi:10.1126/sciadv.1602573

Cited by 65 publications

(173 citation statements)

References 33 publications

(43 reference statements)

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“…treat an immunocompromised child with chronic enteroviral encephalitis 89 , underscoring the potential of drug repurposing in antiviral therapy. The recently elucidated structure of EV-A71 2C 90 will likely encourage soaking or co-crystallization studies and provide more insight into the mode of action of 2C inhibitors, allowing optimization through structure-guided drug design. In addition, inhibitors of host factors, including compounds targeting PI4KB and OSBP, inhibit a broad range of enteroviruses.…”

Section: Heterogeneous Nuclear Ribonucleoprotein Cmentioning

confidence: 99%

The life cycle of non-polio enteroviruses and how to target it

et al. 2018

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The genus Enterovirus (EV) of the family Picornaviridae includes poliovirus, coxsackieviruses, echoviruses, numbered enteroviruses and rhinoviruses. These diverse viruses cause a variety of diseases, including non-specific febrile illness, hand-foot-and-mouth disease, neonatal sepsis-like disease, encephalitis, paralysis and respiratory diseases. In recent years, several non-polio enteroviruses (NPEVs) have emerged as serious public health concerns. These include EV-A71, which has caused epidemics of hand-foot-and-mouth disease in Southeast Asia, and EV-D68, which recently caused a large outbreak of severe lower respiratory tract disease in North America. Infections with these viruses are associated with severe neurological complications. For decades, most research has focused on poliovirus, but in recent years, our knowledge of NPEVs has increased considerably. In this Review, we summarize recent insights from enterovirus research with a special emphasis on NPEVs. We discuss virion structures, host-receptor interactions, viral uncoating and the recent discovery of a universal enterovirus host factor that is involved in viral genome release. Moreover, we briefly explain the mechanisms of viral genome replication, virion assembly and virion release, and describe potential targets for antiviral therapy. We reflect on how these recent discoveries may help the development of antiviral therapies and vaccines.

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Section: Heterogeneous Nuclear Ribonucleoprotein Cmentioning

confidence: 99%

The life cycle of non-polio enteroviruses and how to target it

et al. 2018

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“…Compared with 2D microelectrodes, highly ordered 3D‐structured materials for microbatteries can provide a maximum specific surface area, multiple nanostructures, and shorter ion transmission distances, which lead to a higher areal energy density, superior power density, and outstanding mechanical properties . Furthermore, the facilitation of 3D microbatteries relies on emerging thin‐film deposition techniques . Among these advanced microfabrication strategies, the ALD technique can produce highly protected, uniform, and reproducible atomic‐scale films on high‐aspect‐ratio substrates by precisely control over the thickness, homogeneity, and structure, as shown in Table .…”

Section: Advanced Electrode Engineering For Novel Sibs By Aldmentioning

confidence: 99%

“…Recently, some brief reviews have reported the development of micro‐LIBs by using ALD . Herein, we focus on certain critical studies about ALD‐designed micro‐SIBs.…”

Section: Advanced Electrode Engineering For Novel Sibs By Aldmentioning

confidence: 99%

Electrode Engineering by Atomic Layer Deposition for Sodium‐Ion Batteries: From Traditional to Advanced Batteries

Zhang

et al. 2019

Adv Funct Materials

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Sodium‐ion batteries (SIBs) have emerged as one of the most promising and competitive energy storage systems due to abundant sodium resources and its environmentally friendly features. However, further improvements in the engineering of the SIB electrode/electrolyte interphase—which directly determines the Na‐ion transfer behavior, material structure stability, and sodiation/desodiation property—are highly recommended to meet the continuously increasing requirements for secondary power sources. Reasonably speaking, to promote SIBs, the advanced and controllable interphase/electrode engineering approach exhibits promise by rationally designing the bulk electrode and generating a well‐defined interphase. Atomic layer deposition (ALD) technology, with atomic‐scale deposition, superior uniformity, excellent conformality, and a self‐limiting nature, is thus expected to address the current challenges facing SIBs in terms of low energy density, limited cycling life, and structural instability, and to promote innovations such as multifunctional electrodes and nanostructured materials for advanced SIBs. This review summarizes and discusses the most recent advancements in the interphase engineering of SIBs by ALD via modifying traditional electrodes and designing advanced electrodes (such as 3D, organic, and protected sodium metal electrodes). Furthermore, based on the recent critical progress and current scientific understanding, future perspectives for the engineering of next‐generation SIB electrodes by ALD can be provided.

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“…It is composed of a N-terminal membrane binding domain, a central ATPase domain, a cysteine-rich domain and a C-terminal helical domain [ 20 ]. We recently determined the crystal structure of a soluble portion of 2C helicase from human enterovirus 71 (EV71) [ 21 ], the first high-resolution 2C structure in Picornaviridae . The ATPase domain of EV71 2C exhibits the structural characteristics of superfamily 3 (SF3) helicases.…”

Section: Introductionmentioning

confidence: 99%

Crystal structure of a soluble fragment of poliovirus 2CATPase

et al. 2018

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Poliovirus (PV) 2CATPase is the most studied 2C protein in the Picornaviridae family. It is involved in RNA replication, encapsidation and uncoating and many inhibitors have been found that target PV 2CATPase. Despite numerous investigations to characterize its functions, a high-resolution structure of PV 2C has not yet been determined. We report here the crystal structure of a soluble fragment of PV 2CATPase to 2.55Å, containing an ATPase domain, a zinc finger and a C-terminal helical domain but missing the N-terminal domain. The ATPase domain shares the common structural features with EV71 2C and other Superfamily 3 helicases. The C-terminal cysteine-rich motif folds into a CCCC type zinc finger in which four cysteine ligands and several auxiliary residues assist in zinc binding. By comparing with the known zinc finger fold groups, we found the zinc finger of 2C proteins belong to a new fold group, which we denote the “Enterovirus 2C-like” group. The C-terminus of PV 2CATPase forms an amphipathic helix that occupies a hydrophobic pocket located on an adjacent PV 2CATPase in the crystal lattice. The C-terminus mediated PV 2C-2C interaction promotes self-oligomerization, most likely hexamerization, which is fundamental to the ATPase activity of 2C. The zinc finger is the most structurally diverse feature in 2C proteins. Available structural and virological data suggest that the zinc finger of 2C might confer the specificity of interaction with other proteins. We built a hexameric ring model of PV 2CATPase and visualized the previously identified functional motifs and drug-resistant sites, thus providing a structure framework for antiviral drug development.

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Crystal structure of 2C helicase from enterovirus 71

Abstract: Structure of EV71 2C unveils the structural basis of the functional mechanism of carboxyl terminus–mediated self-oligomerization.

Cited by 65 publications

References 33 publications

The life cycle of non-polio enteroviruses and how to target it

The life cycle of non-polio enteroviruses and how to target it

Electrode Engineering by Atomic Layer Deposition for Sodium‐Ion Batteries: From Traditional to Advanced Batteries

Crystal structure of a soluble fragment of poliovirus 2CATPase

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