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 protein, which packages viral RNA into new virions. We determined a 1.4 Å resolution crystal structure of this protein's N2b domain, revealing a compact, intertwined dimer similar to that of related coronaviruses including SARS-CoV. While the N2b domain forms a dimer in solution, addition of the C-terminal spacer B/N3 domain mediates formation of a homotetramer. 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 self-associates and cooperates with the N2b domain to mediate tetramer formation. Finally, we map the locations of amino acid substitutions in the N protein from over 38,000 SARS-CoV-2 genome sequences. We find that these substitutions are strongly clustered in the protein's N2a linker domain, and that substitutions within the N1...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
Sep 9, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Delyan R HristovKimberly Hamad-Schifferli

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Methods Mentioned

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

Software Mentioned

PRED
PHASER
phenix
Prism
DECA
CCP4
COOT
Jalview
XDS
TRUNCATE

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