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

CUBUK, JASMINE; ALSTON, JHULLIAN J.; INCICCO, J. JEREMÍAS; SINGH, SUKRIT; STUCHELL-BRERETON, MELISSA D.; WARD, MICHAEL D.; ZIMMERMAN, MAXWELL I.; VITHANI, NEHA; GRIFFITH, DANIEL; WAGONER, JASON A.; BOWMAN, GREGORY R.; HALL, KATHLEEN B.; SORANNO, ANDREA; HOLEHOUSE, ALEX S.

NATURE COMMUNICATIONS

Nature Research

Lugar: Londres; Año: 2021 vol. 12

2041-1723

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