tetano
Editor, Senior Moderator
iScience
. 2024 Jan 19;27(2):108976.
doi: 10.1016/j.isci.2024.108976. eCollection 2024 Feb 16. Epitopes recognition of SARS-CoV-2 nucleocapsid RNA binding domain by human monoclonal antibodies
Youngchang Kim[SUP] 1 2 [/SUP], Natalia Maltseva[SUP] 1 2 [/SUP], Christine Tesar[SUP] 1 2 [/SUP], Robert Jedrzejczak[SUP] 1 2 [/SUP], Michael Endres[SUP] 1 2 [/SUP], Heng Ma[SUP] 3 [/SUP], Haley L Dugan[SUP] 4 [/SUP], Christopher T Stamper[SUP] 4 [/SUP], Changsoo Chang[SUP] 1 2 [/SUP], Lei Li[SUP] 4 [/SUP], Siriruk Changrob[SUP] 4 [/SUP], Nai-Ying Zheng[SUP] 4 [/SUP], Min Huang[SUP] 4 [/SUP], Arvind Ramanathan[SUP] 3 [/SUP], Patrick Wilson[SUP] 5 [/SUP], Karolina Michalska[SUP] 1 2 [/SUP], Andrzej Joachimiak[SUP] 1 2 4 [/SUP]
Affiliations
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[SUP]RBD[/SUP]) 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[SUP]RBD[/SUP] were determined providing a continuous model from residue 48 to 173, including RNA binding region and key epitopes. Five structures of NP[SUP]RBD[/SUP] 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.
Keywords: Biochemistry; Immunology; Structural biology.
. 2024 Jan 19;27(2):108976.
doi: 10.1016/j.isci.2024.108976. eCollection 2024 Feb 16. Epitopes recognition of SARS-CoV-2 nucleocapsid RNA binding domain by human monoclonal antibodies
Youngchang Kim[SUP] 1 2 [/SUP], Natalia Maltseva[SUP] 1 2 [/SUP], Christine Tesar[SUP] 1 2 [/SUP], Robert Jedrzejczak[SUP] 1 2 [/SUP], Michael Endres[SUP] 1 2 [/SUP], Heng Ma[SUP] 3 [/SUP], Haley L Dugan[SUP] 4 [/SUP], Christopher T Stamper[SUP] 4 [/SUP], Changsoo Chang[SUP] 1 2 [/SUP], Lei Li[SUP] 4 [/SUP], Siriruk Changrob[SUP] 4 [/SUP], Nai-Ying Zheng[SUP] 4 [/SUP], Min Huang[SUP] 4 [/SUP], Arvind Ramanathan[SUP] 3 [/SUP], Patrick Wilson[SUP] 5 [/SUP], Karolina Michalska[SUP] 1 2 [/SUP], Andrzej Joachimiak[SUP] 1 2 4 [/SUP]
Affiliations
- PMID: 38327783
- PMCID: PMC10847736
- DOI: 10.1016/j.isci.2024.108976
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[SUP]RBD[/SUP]) 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[SUP]RBD[/SUP] were determined providing a continuous model from residue 48 to 173, including RNA binding region and key epitopes. Five structures of NP[SUP]RBD[/SUP] 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.
Keywords: Biochemistry; Immunology; Structural biology.