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

BioRxiv : the Preprint Server for Biology
Jasmine CubukAlex S Holehouse

Abstract

The SARS-CoV-2 nucleocapsid (N) protein is an abundant RNA binding protein that plays a variety of roles in the viral life cycle including replication, transcription, and genome packaging. Despite its critical and multifunctional nature, the molecular details that underlie how N protein mediates these functions are poorly understood. Here we combine single-molecule spectroscopy with all-atom simulations to uncover the molecular details that contribute to the function of SARS-CoV-2 N protein. N protein contains three intrinsically disordered regions and two folded domains. All three disordered regions are highly dynamic and contain regions of transient helicity that appear to act as local binding interfaces for protein-protein or protein-RNA interactions. The two folded domains do not significantly interact with one another, such that full-length N protein is a flexible and multivalent RNA binding protein. As observed for other proteins with similar molecular features, we found that N protein undergoes liquid-liquid phase separation when mixed with RNA. Polymer models predict that the same multivalent interactions that drive phase separation also engender RNA compaction. We propose a simple model in which symmetry breaking throu...Continue Reading

Citations

Oct 18, 2020·Nucleic Acids Research·Andrea VandelliGian Gaetano Tartaglia
Oct 21, 2020·Emerging Topics in Life Sciences·Erik W Martin, Alex S Holehouse
Dec 15, 2020·Wellcome Open Research·Stefan BressonDavid Tollervey
Oct 30, 2020·Frontiers in Immunology·Gideon Schreiber
Dec 29, 2020·Biochemical Society Transactions·Ilaria Manfredonia, Danny Incarnato
Mar 7, 2021·Viruses·Temitope Akhigbe EtiborMaria João Amorim

Methods Mentioned

BETA
FRET
X-ray
Fluorescence
FCS
dissection
NMR
electron tomography

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