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

Zhaoming Su, Chao Wu, Liuqing Shi, Priya Luthra, Grigore D. Pintilie, Britney Johnson, Justin R. Porter, Peng Ge, Muyuan Chen, Gai Liu, Thomas E. Frederick, Jennifer M. Binning, Gregory R. Bowman, Z. Hong Zhou, Christopher F. Basler, Michael L. Gross, Daisy W. Leung, Wah Chiu, Gaya K. Amarasinghe

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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. Biochemical, biophysical, and functional validation of a 5.8 Å cryo-EM structure of the Ebola virus nucleoprotein provides insight into filovirus nucleocapsid formation.

Original languageEnglish
Pages (from-to)966-978.e12
JournalCell
Volume172
Issue number5
DOIs
StatePublished - Feb 22 2018

Keywords

  • Ebola virus
  • cryo-EM
  • nucleocapsid
  • nucleoprotein
  • viral RNA synthesis

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    Su, Z., Wu, C., Shi, L., Luthra, P., Pintilie, G. D., Johnson, B., Porter, J. R., Ge, P., Chen, M., Liu, G., Frederick, T. E., Binning, J. M., Bowman, G. R., Zhou, Z. H., Basler, C. F., Gross, M. L., Leung, D. W., Chiu, W., & Amarasinghe, G. K. (2018). Electron Cryo-microscopy Structure of Ebola Virus Nucleoprotein Reveals a Mechanism for Nucleocapsid-like Assembly. Cell, 172(5), 966-978.e12. https://doi.org/10.1016/j.cell.2018.02.009