The nucleocapsid protein (N) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encapsidates the viral genome and is essential for the replication of this important human pathogen. The central region of the protein is highly disordered, and is found to be hyperphosphorylated in infected cells, a modification that changes the function of the protein during the viral cycle. Remarkably the protein is not phosphorylated in the infectious particle (the virion).
Researchers at the IBS (Protein Dynamics and Flexibility by NMR Group) have investigated the switch in conformational behaviour induced by phosphorylation, that they observe in real time, and at atomic resolution, using NMR spectroscopy. They reveal that this chemical modificaiton results in inhibition and release of RNA binding, suggesting a role in unpacking of the viral particle upon infection.
A specific phosphorylation-dependent conformational switch in SARS-CoV-2 nucleocapsid protein inhibits RNA binding. Botova M, Camacho-Zarco AR, Tognetti J, Mamigonian Bessa L, Guseva S, Mikkola E, Salvi N, Maurin D, Herrmann T, Blackledge M. Science Advances 2024 ; 10(31):eaax2323. doi : 10.1126/sciadv.aax2323.
Contact : Martin Blackledge, chercheur CEA de l’IBS (Groupe Flexibilité et Dynamique des Protéines par RMN)