7STR

Crystal Structure of Human Fab S24-1063 in the Complex with the N-teminal Domain of Nucleocapsid Protein from SARS CoV-2

Summary for 7STR

• Entry DOI: 10.2210/pdb7str/pdb
• Descriptor: Fab S24-1063, Light chain, Fab S24-1063, Heavy chain, Nucleoprotein, ... (5 entities in total)
• Functional Keywords: sars coronavirus 2, nucleocapsid protein, human antibody fab, covid-19, structural genomics, center for structural genomics of infectious diseases, csgid, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 61821.77

Authors

Kim, Y.,Maltseva, N.,Tesar, C.,Jedrzejczak, R.,Dugan, H.,Stamper, C.,Wilson, P.,Joachimiak, A.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2021-11-15, release date: 2022-08-10, Last modification date: 2024-10-09)

Primary citation

Kim, Y.,Maltseva, N.,Tesar, C.,Jedrzejczak, R.,Endres, M.,Ma, H.,Dugan, H.L.,Stamper, C.T.,Chang, C.,Li, L.,Changrob, S.,Zheng, N.Y.,Huang, M.,Ramanathan, A.,Wilson, P.,Michalska, K.,Joachimiak, A.
Epitopes recognition of SARS-CoV-2 nucleocapsid RNA binding domain by human monoclonal antibodies.
Iscience, 27:108976-108976, 2024

PubMed Abstract: Coronavirus nucleocapsid protein (NP) of SARS-CoV-2 plays a central role in many functions important for virus proliferation including packaging and protecting genomic RNA. The protein shares sequence, structure, and architecture with nucleocapsid proteins from betacoronaviruses. The N-terminal domain (NP) binds RNA and the C-terminal domain is responsible for dimerization. After infection, NP is highly expressed and triggers robust host immune response. The anti-NP antibodies are not protective and not neutralizing but can effectively detect viral proliferation soon after infection. Two structures of SARS-CoV-2 NP were determined providing a continuous model from residue 48 to 173, including RNA binding region and key epitopes. Five structures of NP complexes with human mAbs were isolated using an antigen-bait sorting. Complexes revealed a distinct complement-determining regions and unique sets of epitope recognition. This may assist in the early detection of pathogens and designing peptide-based vaccines. Mutations that significantly increase viral load were mapped on developed, full length NP model, likely impacting interactions with host proteins and viral RNA.

PubMed: 38327783
DOI: 10.1016/j.isci.2024.108976

Experimental method

X-RAY DIFFRACTION (1.5 Å)