Insight into the Ebola virus nucleocapsid assembly mechanism: crystal structure of Ebola virus nucleoprotein core domain at 1.8 ? resolution

Shishang Dong, Peng Yang, Guobang Li, Baocheng Liu, Wenming Wang, Xiang Liu, Boran Xia, Cheng Yang, Zhiyong Lou, Yu Guo, Zihe Rao

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Protein Cell ›› 2015, Vol. 6 ›› Issue (5) : 351-362. DOI: 10.1007/s13238-015-0163-3
RESEARCH ARTICLE

Insight into the Ebola virus nucleocapsid assembly mechanism: crystal structure of Ebola virus nucleoprotein core domain at 1.8 ? resolution

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Abstract

Ebola virus (EBOV) is a key member of Filoviridae family and causes severe human infectious diseases with high morbidity and mortality. As a typical negative-sense single-stranded RNA (-ssRNA) viruses, EBOV possess a nucleocapsid protein (NP) to facilitate genomic RNA encapsidation to form viral ribonucleoprotein complex (RNP) together with genome RNA and polymerase, which plays the most essential role in virus proliferation cycle. However, the mechanism of EBOV RNP formation remains unclear. In this work, we solved the high resolution structure of core domain of EBOV NP. The polypeptide of EBOV NP core domain (NPcore) possesses an N-lobe and C-lobe to clamp a RNA binding groove, presenting similarities with the structures of the other reported viral NPs encoded by the members from Mononegavirales order. Most strikingly, a hydrophobic pocket at the surface of the C-lobe is occupied by an α-helix of EBOV NPcore itself, which is highly conserved among filoviridae family. Combined with other biochemical and biophysical evidences, our results provides great potential for understanding the mechanism underlying EBOV RNP formation via the mobility of EBOV NP element and enables the development of antiviral therapies targeting EBOV RNP formation.

Keywords

Filoviridae / Ebola virus / nucleoprotein / nucleocapsid / crystal structure / assembly mechanism

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Shishang Dong, Peng Yang, Guobang Li, Baocheng Liu, Wenming Wang, Xiang Liu, Boran Xia, Cheng Yang, Zhiyong Lou, Yu Guo, Zihe Rao. Insight into the Ebola virus nucleocapsid assembly mechanism: crystal structure of Ebola virus nucleoprotein core domain at 1.8 Å resolution. Protein Cell, 2015, 6(5): 351‒362 https://doi.org/10.1007/s13238-015-0163-3

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2014 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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