Replication Data for: A conserved oligomerization domain in the disordered linker of coronavirus nucleocapsid proteins

The datasets provide source data for this study, sorted by topic and technique. After expanding the archives additional metadata can be found. Abstract: The nucleocapsid (N-)protein of SARS-CoV-2 is one of the most abundant and multi-functional viral proteins. It is composed of two folded domains for nucleic acid binding and dimerization, respectively, that are linked and flanked by large segments of intrinsically disordered regions (IDRs). N-protein has a key role in viral assembly and scaffolding of the viral RNA. It promotes liquid-liquid phase separation (LLPS), forming dense droplets that support the assembly of ribonucleoprotein particles with as-of-yet unknown macromolecular architecture. Here we describe a heretofore unknown oligomerization site that contributes to LLPS, is required for the assembly of higher-order protein-nucleic acid complexes, and is coupled to large-scale conformational changes of N-protein upon nucleic acid binding. The self-association interface is located in the leucine-rich sequence (LRS) of the disordered linker and formed by transient helices assembling into largely trimeric coiled-coils. Detailed structural and biophysical analyses of LRS and LRS mutant peptides and full-length N-proteins reveal key residues stabilizing hydrophobic and electrostatic interactions between adjacent helices. These are highly protected against mutations in viable SARS-CoV-2 genomes and conserved across related coronaviruses, thus presenting a new target for antiviral therapeutics.