7JIE
Structure of GII.4 P-domain in Complex with NORO-320 FAB
Summary for 7JIE
| Entry DOI | 10.2210/pdb7jie/pdb |
| Descriptor | VP1, IgA Fab Heavy Chain, IgA Fab Light Chain, ... (4 entities in total) |
| Functional Keywords | antibody, complex, viral capsid protein, neutralization, viral protein |
| Biological source | Norovirus Hu/GII.4/Sydney/NSW0514/2012/AU More |
| Total number of polymer chains | 6 |
| Total formula weight | 166277.76 |
| Authors | Salmen, W.,Hu, L.,Prasad, B. (deposition date: 2020-07-23, release date: 2021-06-30, Last modification date: 2024-10-23) |
| Primary citation | Alvarado, G.,Salmen, W.,Ettayebi, K.,Hu, L.,Sankaran, B.,Estes, M.K.,Venkataram Prasad, B.V.,Crowe Jr., J.E. Broadly cross-reactive human antibodies that inhibit genogroup I and II noroviruses. Nat Commun, 12:4320-4320, 2021 Cited by PubMed Abstract: The rational development of norovirus vaccine candidates requires a deep understanding of the antigenic diversity and mechanisms of neutralization of the virus. Here, we isolate and characterize a panel of broadly cross-reactive naturally occurring human monoclonal IgMs, IgAs and IgGs reactive with human norovirus (HuNoV) genogroup I or II (GI or GII). We note three binding patterns and identify monoclonal antibodies (mAbs) that neutralize at least one GI or GII HuNoV strain when using a histo-blood group antigen (HBGA) blocking assay. The HBGA blocking assay and a virus neutralization assay using human intestinal enteroids reveal that the GII-specific mAb NORO-320, mediates HBGA blocking and neutralization of multiple GII genotypes. The Fab form of NORO-320 neutralizes GII.4 infection more potently than the mAb, however, does not block HBGA binding. The crystal structure of NORO-320 Fab in complex with GII.4 P-domain shows that the antibody recognizes a highly conserved region in the P-domain distant from the HBGA binding site. Dynamic light scattering analysis of GII.4 virus-like particles with mAb NORO-320 shows severe aggregation, suggesting neutralization is by steric hindrance caused by multivalent cross-linking. Aggregation was not observed with the Fab form of NORO-320, suggesting that this clone also has additional inhibitory features. PubMed: 34262046DOI: 10.1038/s41467-021-24649-w PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.254 Å) |
Structure validation
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