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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/NCAP_SARS2 NCAP_SARS2]] Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane protein M. Plays an important role in enhancing the efficiency of subgenomic viral RNA transcription as well as viral replication. | [[http://www.uniprot.org/uniprot/NCAP_SARS2 NCAP_SARS2]] Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane protein M. Plays an important role in enhancing the efficiency of subgenomic viral RNA transcription as well as viral replication. | ||
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== Publication Abstract from PubMed == | |||
The COVID-2019 pandemic is the most severe acute public health threat of the twenty-first century. To properly address this crisis with both robust testing and novel treatments, we require a deep understanding of the life cycle of the causative agent, the SARS-CoV-2 coronavirus. Here, we examine the architecture and self-assembly properties of the SARS-CoV-2 nucleocapsid (N) protein, which binds viral RNA and assembles into a filament that is packaged into new virions. We determined a 1.4 A resolution crystal structure of this protein's N2b domain, revealing a compact, intertwined dimer very similar to that of related coronaviruses SARS-CoV and MERS-CoV. Using size exclusion chromatography and multi-angle light scattering, we find that this domain forms a dimer in solution, and that addition of the C-terminal spacer B/N3 domain mediates tetramer formation. Using hydrogen-deuterium exchange mass spectrometry, we find evidence that at least part of this putatively disordered domain is structured, potentially forming an alpha-helix that either self-associates or docks against the N2b domain to mediate tetramer formation. Finally, we map the locations of over 4,400 individual amino acid substitutions in the N protein from (~)17,000 SARS-CoV-2 genome sequences, and find that they are strongly clustered in the protein's N2a linker domain. The nearly 300 substitutions identified within the N1b and N2b domains cluster away from their functional RNA binding and dimerization interfaces. Overall, this work reveals the architecture and self-assembly properties of a key protein in the SARS-CoV-2 life cycle. As the N protein is a common target of patient antibodies, this work will also benefit ongoing efforts to develop robust and specific serological tests, and could also benefit the analysis of patient-derived antibodies. | |||
Architecture and self-assembly of the SARS-CoV-2 nucleocapsid protein.,Ye Q, West AMV, Silletti S, Corbett KD bioRxiv. 2020 May 17. doi: 10.1101/2020.05.17.100685. PMID:32511359<ref>PMID:32511359</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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== References == | |||
<references/> | |||
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</StructureSection> | </StructureSection> | ||
Revision as of 10:17, 25 June 2020
Structure of SARS-CoV-2 Nucleocapsid dimerization domain, P21 formStructure of SARS-CoV-2 Nucleocapsid dimerization domain, P21 form
Structural highlights
Function[NCAP_SARS2] Packages the positive strand viral genome RNA into a helical ribonucleocapsid (RNP) and plays a fundamental role during virion assembly through its interactions with the viral genome and membrane protein M. Plays an important role in enhancing the efficiency of subgenomic viral RNA transcription as well as viral replication. Publication Abstract from PubMedThe COVID-2019 pandemic is the most severe acute public health threat of the twenty-first century. To properly address this crisis with both robust testing and novel treatments, we require a deep understanding of the life cycle of the causative agent, the SARS-CoV-2 coronavirus. Here, we examine the architecture and self-assembly properties of the SARS-CoV-2 nucleocapsid (N) protein, which binds viral RNA and assembles into a filament that is packaged into new virions. We determined a 1.4 A resolution crystal structure of this protein's N2b domain, revealing a compact, intertwined dimer very similar to that of related coronaviruses SARS-CoV and MERS-CoV. Using size exclusion chromatography and multi-angle light scattering, we find that this domain forms a dimer in solution, and that addition of the C-terminal spacer B/N3 domain mediates tetramer formation. Using hydrogen-deuterium exchange mass spectrometry, we find evidence that at least part of this putatively disordered domain is structured, potentially forming an alpha-helix that either self-associates or docks against the N2b domain to mediate tetramer formation. Finally, we map the locations of over 4,400 individual amino acid substitutions in the N protein from (~)17,000 SARS-CoV-2 genome sequences, and find that they are strongly clustered in the protein's N2a linker domain. The nearly 300 substitutions identified within the N1b and N2b domains cluster away from their functional RNA binding and dimerization interfaces. Overall, this work reveals the architecture and self-assembly properties of a key protein in the SARS-CoV-2 life cycle. As the N protein is a common target of patient antibodies, this work will also benefit ongoing efforts to develop robust and specific serological tests, and could also benefit the analysis of patient-derived antibodies. Architecture and self-assembly of the SARS-CoV-2 nucleocapsid protein.,Ye Q, West AMV, Silletti S, Corbett KD bioRxiv. 2020 May 17. doi: 10.1101/2020.05.17.100685. PMID:32511359[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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