Phosphorylation Changes SARS-CoV-2 Nucleocapsid Protein's Structural Dynamics and Its Interaction With RNA
Stefan Loonen (Kavli institute of nanoscience Delft, TU Delft - BN/Nikolina Šoštaric Lab)
Lina van Steenis (Student TU Delft)
M.S. Bauer (TU Delft - BN/Bionanoscience, TU Delft - BN/Marianne Bauer Lab, Kavli institute of nanoscience Delft)
Nikolina Šoštarić (Kavli institute of nanoscience Delft, TU Delft - BN/Nikolina Šoštaric Lab)
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Abstract
The SARS-CoV-2 nucleocapsid protein, or N-protein, is a structural protein that plays an important role in the SARS-CoV-2 life cycle. The N-protein takes part in the regulation of viral RNA replication and drives highly specific packaging of full-length genomic RNA prior to virion formation. One regulatory mechanism that is proposed to drive the switch between these two operating modes is the phosphorylation state of the N-protein. Here, we assess the dynamic behavior of non-phosphorylated and phosphorylated versions of the N-protein homodimer through atomistic molecular dynamics simulations. We show that the introduction of phosphorylation yields a more dynamic protein structure and decreases the binding affinity between the N-protein and RNA. Furthermore, we find that secondary structure is essential for the preferential binding of particular RNA elements from the 5′ UTR of the viral genome to the N-terminal domain of the N-protein. Altogether, we provide detailed molecular insights into N-protein dynamics, N-protein:RNA interactions, and phosphorylation. Our results corroborate the hypothesis that phosphorylation of the N-protein serves as a regulatory mechanism that determines N-protein function.
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