9KUR
Crystal structure of mAb nCoV400Fab with SARS-CoV-2 N-CTD Complex
Summary for 9KUR
| Entry DOI | 10.2210/pdb9kur/pdb |
| Descriptor | Nucleoprotein, 400Fab Heavy chain, 400Fab Light chain, ... (4 entities in total) |
| Functional Keywords | coronavirus, sars-cov-2, nucleocapsid protein, c-terminal dimerization domain, viral protein |
| Biological source | Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2) More |
| Total number of polymer chains | 6 |
| Total formula weight | 121895.45 |
| Authors | |
| Primary citation | Xue, S.,He, S.,Huang, Z.,Yang, M.,Hu, G.,Chen, X.,Chen, Q.,Zhou, W.,Lin, S.,Chen, S. Structural basis of a human antibody targeting SARS-CoV-2 nucleocapsid protein dimerization domain and interfering with RNA-binding. Commun Biol, 8:1248-1248, 2025 Cited by PubMed Abstract: The transition of SARS-CoV-2 into a recurrent, seasonal pathogen has underscored the need for the induction of durable immune protection. The nucleocapsid (N) protein is regarded as a promising complementary target for therapeutic and vaccine strategies, owing to its structural robustness, clinical relevance, and ability to elicit critical immune response. Within the N protein, the C-terminal domain (N-CTD) plays a pivotal role in assembly of viral RNA (vRNA)-N protein complexes, and in facilitating liquid-liquid phase separation (LLPS) through specific interactions with RNA on its dimerization surface. Despite its functional importance, the molecular mechanisms by which the RNA-binding surface of this domain can be selectively targeted by inhibitors remain poorly defined. Herein, we report a 2.06 Å crystal structure of the SARS-CoV-2 N-CTD in complex with nCoV400Fab, a human monoclonal antibody derived from single B-cell screening. The structure reveals that nCoV400Fab engages multiple basic residues on the RNA-binding surface, forming a steric blockade that hinders vRNA binding. Functional assays demonstrate that nCoV400Fab disrupts both viral ribonucleoprotein (vRNP) assembly and RNA-induced condensate formation. Together, these findings define a structural mechanism by which a human antibody disrupts the RNA-binding surface of N-CTD, laying the foundation for the development of macromolecular inhibitors. PubMed: 40830575DOI: 10.1038/s42003-025-08648-x PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.06 Å) |
Structure validation
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