Electron cryo-microscopy structure of ebola virus nucleoprotein reveals a mechanism for nucleocapsid-like assembly

• Autores: Zhaoming Su, Chao Wu, Liuqing Shi
• Localización: Cell, ISSN 0092-8674, Vol. 172, Nº. 5, 2018, págs. 966-978
• Idioma: inglés
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• Resumen

  • 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.