TY - JOUR
T1 - The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA
AU - Cubuk, Jasmine
AU - Alston, Jhullian J.
AU - Incicco, J. Jeremías
AU - Singh, Sukrit
AU - Stuchell-Brereton, Melissa D.
AU - Ward, Michael D.
AU - Zimmerman, Maxwell I.
AU - Vithani, Neha
AU - Griffith, Daniel
AU - Wagoner, Jason A.
AU - Bowman, Gregory R.
AU - Hall, Kathleen B.
AU - Soranno, Andrea
AU - Holehouse, Alex S.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85103544468&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-21953-3
DO - 10.1038/s41467-021-21953-3
M3 - Article
C2 - 33782395
AN - SCOPUS:85103544468
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1936
ER -