Atomic-Resolution Structure of SARS-CoV-2 Nucleocapsid Protein N-Terminal Domain
Sucharita Sarkar, Brent Runge, Ryan W. Russell, Kumar Tekwani Movellan, Daniel Calero, Somayeh Zeinalilathori, Caitlin M. Quinn, Manman Lu, Guillermo Calero, Angela M. Gronenborn, Tatyana Polenova
Abstract
The nucleocapsid (N) protein is one of the four structural proteins of the SARS-CoV-2 virus and plays a crucial role in viral genome organization and, hence, replication and pathogenicity. The N-terminal domain (NNTD) binds to the genomic RNA and thus comprises a potential target for inhibitor and vaccine development. We determined the atomic-resolution structure of crystalline NNTD by integrating solid-state magic angle spinning (MAS) NMR and X-ray diffraction. Our combined approach provides atomic details of protein packing interfaces as well as information about flexible regions as the N- and C-termini and the functionally important RNA binding, β-hairpin loop. In addition, ultrafast (100 kHz) MAS 1H-detected experiments permitted the assignment of side-chain proton chemical shifts not available by other means. The present structure offers guidance for designing therapeutic interventions against the SARS-CoV-2 infection.