Architecture and self-assembly of the SARS-CoV-2 nucleocapsid protein.

BioRxiv : the Preprint Server for Biology
Q. YeKevin D. Corbett

Abstract

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 Å 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 α-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-...Continue Reading

Citations

Sep 15, 2020·World Journal of Virology·Mohammad Khalid Parvez
Nov 29, 2020·Nature Communications·Adriana SavastanoMarkus Zweckstetter
Jan 20, 2021·Journal of Proteome Research·Paige HaasRuth Hüttenhain
Feb 8, 2021·Stem Cell Research·Gangyu SunZhizhi Wang

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Methods Mentioned

BETA
two-hybrid
NMR
gel filtration
Size exclusion chromatography
Size
light scattering
PCR
size-exclusion
light

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