The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA

• DOI: 10.1038/s41467-021-21953-3
• Publication Date: 2021-03-29T10:04:22Z
• Authors: Jasmine Cubuk; Jhullian J. Alston; J. Jeremías Incicco; Sukrit Singh; Melissa D. Stuche...; Michael D. Ward; Maxwell I. Zimmerman; Neha Vithani; Daniel Griffith; Jason A. Wagoner; Gregory R. Bowman; Kathleen B. Hall; Andrea Soranno; Alex S. Holehouse
• Keywords: 0301 basic medicine; 0303 health sciences; Binding Sites; Protein Conformation; SARS-CoV-2; Science; Q; COVID-19; Molecular Dynamics Simulation; Phosphoproteins; Article; 3. Good health; 03 medical and health sciences; Protein Domains; Coronavirus Nucleocapsid Proteins; RNA, Viral; Dimerization

The SARS-CoV-2 nucleocapsid (N) protein is an abundant RNA-binding critical for viral genome packaging, yet the molecular details that underlie this process are poorly understood. Here we combine single-molecule spectroscopy with all-atom simulations to uncover contribute N function. contains three dynamic disordered regions house putative transiently-helical binding motifs. two folded domains interact minimally such full-length a flexible and multivalent protein. also undergoes liquid-liquid phase separation when mixed RNA, polymer theory predicts same interactions drive engender RNA compaction. We offer simple symmetry-breaking model provides plausible route through which single-genome condensation preferentially occurs over separation, suggesting offers convenient macroscopic readout of key nanoscopic interaction.