Combining simulations and single-molecule fluorescence spectroscopy to understand SARS-CoV-2 nucleocapsid protein RNA interaction.

Abstract

SARS-CoV-2 causes the respiratory disease COVID-19 that has resulted in a worldwide pandemic. An outstanding question revolves around how SARS-CoV-2 and related coronaviruses package their relatively long 30 kb genomes into a relatively small (<100 nm) virion. Genome packaging is driven by the nucleocapsid protein (N), a five-domain protein that consists of an intrinsically disordered N-terminal domain (NTD), folded RNA binding domain (RBD), disordered linker domain, folded dimerization domain, and a C-terminal disordered domain. This domain architecture is conserved in coronaviruses, hinting at the importance of interspersed disordered and folded domains in mediating N-protein biological function.