Characterizing nucleic acid interactions with the N-Terminal binding domain of the SARS-CoV-2 nucleocapsid protein

Abstract

The SARS-CoV-2 Nucleocapsid (N) protein is responsible for condensation of the viral genome. Quantifying the mechanisms controlling nucleic acid binding is a key step to understand how such condensation is realized. We have previously shown that the three disordered regions flanking the RNA binding domain (RBD) and dimerization domain are highly dynamic. Here, we focus on the role of the RBD and the disordered N-Terminal Domain (NTD) tail. Using single-molecule Foerster Resonance Energy Transfer, we quantify both binding of the nucleic acids and concomitant conformational changes occurring in the disordered region.