Electron Cryo-microscopy Structure of Ebola Virus Nucleoprotein Reveals a Mechanism for Nucleocapsid-like Assembly

Ebola virus nucleoprotein (eNP) assembles into higher-ordered structures that form the viral nucleocapsid (NC) and serve as the scaffold for viral RNA synthesis. However, molecular insights into the NC assembly process are lacking. Using a hybrid approach, we characterized the NC-like assembly of eN...

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Bibliographic Details
Published in:Cell Vol. 172; no. 5; p. 966
Main Authors: Su, Zhaoming, Wu, Chao, Shi, Liuqing, Luthra, Priya, Pintilie, Grigore D, Johnson, Britney, Porter, Justin R, Ge, Peng, Chen, Muyuan, Liu, Gai, Frederick, Thomas E, Binning, Jennifer M, Bowman, Gregory R, Zhou, Z Hong, Basler, Christopher F, Gross, Michael L, Leung, Daisy W, Chiu, Wah, Amarasinghe, Gaya K
Format: Journal Article
Language:English
Published: United States 22.02.2018
Subjects:
Cryoelectron Microscopy
Ebolavirus - physiology
Ebolavirus - ultrastructure
Models, Biological
Mutant Proteins - chemistry
Mutation - genetics
Nucleocapsid - ultrastructure
Nucleoproteins - chemistry
Nucleoproteins - ultrastructure
Protein Multimerization
Protein Structure, Secondary
Protein Subunits - chemistry
Protein Subunits - metabolism
RNA, Viral - biosynthesis
RNA, Viral - chemistry
RNA, Viral - metabolism
Virus Assembly
Ebola virus
nucleocapsid
nucleoprotein
viral RNA synthesis
cryo-EM
ISSN:1097-4172, 1097-4172
Online Access:Get more information
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Summary:Ebola virus nucleoprotein (eNP) assembles into higher-ordered structures that form the viral nucleocapsid (NC) and serve as the scaffold for viral RNA synthesis. However, molecular insights into the NC assembly process are lacking. Using a hybrid approach, we characterized the NC-like assembly of eNP, identified novel regulatory elements, and described how these elements impact function. We generated a three-dimensional structure of the eNP NC-like assembly at 5.8 Å using electron cryo-microscopy and identified a new regulatory role for eNP helices α22-α23. Biochemical, biophysical, and mutational analyses revealed that inter-eNP contacts within α22-α23 are critical for viral NC assembly and regulate viral RNA synthesis. These observations suggest that the N terminus and α22-α23 of eNP function as context-dependent regulatory modules (CDRMs). Our current study provides a framework for a structural mechanism for NC-like assembly and a new therapeutic target.
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ISSN:1097-4172
1097-4172
DOI:10.1016/j.cell.2018.02.009