1. The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA.
- Author
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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, and Holehouse, Alex S.
- Subjects
SARS-CoV-2 ,RNA-binding proteins ,PHASE separation ,RNA ,VIRAL genomes - Abstract
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. SARS-CoV-2 nucleocapsid (N) protein is responsible for viral genome packaging. Here the authors employ single-molecule spectroscopy with all-atom simulations to provide the molecular details of N protein and show that it undergoes phase separation with RNA. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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