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

Nature Communications
J. CubukAlex S Holehouse

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.

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Citations

Jun 10, 2021·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Yamilka DíazUNKNOWN Gorgas COVID19 Team

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