Contributions of the N‐terminal intrinsically disordered region of the severe acute respiratory syndrome coronavirus 2 nucleocapsid protein to RNA‐induced phase separation
2022 | journal article. A publication with affiliation to the University of Göttingen.
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Contributions of the N‐terminal intrinsically disordered region of the severe acute respiratory syndrome coronavirus 2 nucleocapsid protein to RNA‐induced phase separation
Zachrdla, M.; Savastano, A. ; Ibáñez de Opakua, A.; Cima‐Omori, M. & Zweckstetter, M. (2022)
Protein Science, 31(9). DOI: https://doi.org/10.1002/pro.4409
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Details
- Authors
- Zachrdla, Milan; Savastano, Adriana ; Ibáñez de Opakua, Alain; Cima‐Omori, Maria‐Sol; Zweckstetter, Markus
- Abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein is an essential structural component of mature virions, encapsulating the genomic RNA and modulating RNA transcription and replication. Several of its activities might be associated with the protein's ability to undergo liquid– liquid phase separation. NSARS-CoV-2 contains an intrinsically disordered region at its N-terminus (NTE) that can be phosphorylated and is affected by mutations found in human COVID-19 infections, including in the Omicron variant of concern. Here, we show that NTE deletion decreases the range of RNA concentrations that can induce phase separation of NSARS-CoV-2. In addition, deletion of the prion-like NTE allows NSARS-CoV-2 droplets to retain their liquid-like nature during incubation. We further demonstrate that RNAbinding engages multiple parts of the NTE and changes NTE's structural properties. The results form the foundation to characterize the impact of N-terminal mutations and post-translational modifications on the molecular properties of the SARS-CoV-2 nucleocapsid protein. Statement: The nucleocapsid protein of SARS-CoV-2 plays an important role in both genome packaging and viral replication upon host infection. Replication has been associated with RNA-induced liquid–liquid phase separation of the nucleocapsid protein. We present insights into the role of the N-terminal part of the nucleocapsid protein in the protein's RNA-mediated liquid–liquid phase separation.
- Issue Date
- 2022
- Journal
- Protein Science
- Organization
- Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) ; Max-Planck-Institut für Multidisziplinäre Naturwissenschaften
- ISSN
- 0961-8368
- eISSN
- 1469-896X
- Language
- English
- Sponsor
- H2020 European Research Council https://doi.org/10.13039/100010663