Jasmine Cubuk, Jhullian J Alston, J. Incicco, Sukrit Singh, Melissa D. Stuchell-Brereton, Michael D. Ward, M. I. Zimmerman, N. Vithani, Daniel Griffith, Jason A Wagoner, G. Bowman, K. Hall, Andrea Soranno, A. Holehouse
bioRxiv : the preprint server for biology, 2020
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.
Cited by 55 publications.
Field of study: Biology