Abstract
The nucleocapsid protein of the SARS-CoV-2 virus comprises two RNA-binding domains and three regions that are intrinsically disordered. While the structures of the RNA-binding domains have been solved using protein crystallography and NMR, current knowledge of the conformations of the full-length nucleocapsid protein is rather limited. To fill in this knowledge gap, we combined coarse-grained molecular simulations with data from small-angle X-ray scattering (SAXS) experiments using the ensemble refinement of SAXS (EROS) method. Our results show that the dimer of the full-length nucleocapsid protein exhibits large conformational fluctuations with its radius of gyration ranging from about 4 to 8 nm. The RNA-binding domains do not make direct contacts. The disordered region that links these two domains comprises a hydrophobic α-helix which makes frequent and nonspecific contacts with the RNA-binding domains. Each of the intrinsically disordered regions adopts conformations that are locally compact, yet on average, much more extended than Gaussian chains of equivalent lengths. We offer a detailed picture of the conformational ensemble of the nucleocapsid protein dimer under near-physiological conditions, which will be important for understanding the nucleocapsid assembly process.
Keywords: EROS; Nucleocapsid; SARS-CoV-2; SAXS.
【저자키워드】 SARS-CoV-2, nucleocapsid, EROS, SAXS., 【초록키워드】 Structure, knowledge, SARS-CoV-2 virus, nucleocapsid protein, Protein, Region, nucleocapsid, experiment, NMR, Molecular simulation, EROS, conformations, structures, Contact, domains, domain, average, conformation, dimer, Each, hydrophobic, gyration, radius of gyration, full-length, while, offer, fluctuation, α-helix, conformational, conditions, exhibit, intrinsically, X-ray scattering, nonspecific, the SARS-CoV-2 virus, 【제목키워드】 Protein, Molecular simulation, full-length SARS-CoV-2,