6N81
Crystal structure of GII.4 2002 norovirus P domain in complex with cross-reactive human antibody A1227
Summary for 6N81
| Entry DOI | 10.2210/pdb6n81/pdb |
| Descriptor | Major capsid protein, A1227 Fab light chain, A1227 Fab heavy chain, ... (4 entities in total) |
| Functional Keywords | norovirus, human antibody, complex, fab, immune system |
| Biological source | Norovirus Hu/GII.4/Farmington Hills/2004/USA More |
| Total number of polymer chains | 6 |
| Total formula weight | 163922.68 |
| Authors | Changela, A.,Verardi, R.,Kwong, P.D. (deposition date: 2018-11-28, release date: 2019-06-19, Last modification date: 2024-10-30) |
| Primary citation | Lindesmith, L.C.,McDaniel, J.R.,Changela, A.,Verardi, R.,Kerr, S.A.,Costantini, V.,Brewer-Jensen, P.D.,Mallory, M.L.,Voss, W.N.,Boutz, D.R.,Blazeck, J.J.,Ippolito, G.C.,Vinje, J.,Kwong, P.D.,Georgiou, G.,Baric, R.S. Sera Antibody Repertoire Analyses Reveal Mechanisms of Broad and Pandemic Strain Neutralizing Responses after Human Norovirus Vaccination. Immunity, 50:1530-1541.e8, 2019 Cited by PubMed Abstract: Rapidly evolving RNA viruses, such as the GII.4 strain of human norovirus (HuNoV), and their vaccines elicit complex serological responses associated with previous exposure. Specific correlates of protection, moreover, remain poorly understood. Here, we report the GII.4-serological antibody repertoire-pre- and post-vaccination-and select several antibody clonotypes for epitope and structural analysis. The humoral response was dominated by GII.4-specific antibodies that blocked ancestral strains or by antibodies that bound to divergent genotypes and did not block viral-entry-ligand interactions. However, one antibody, A1431, showed broad blockade toward tested GII.4 strains and neutralized the pandemic GII.P16-GII.4 Sydney strain. Structural mapping revealed conserved epitopes, which were occluded on the virion or partially exposed, allowing for broad blockade with neutralizing activity. Overall, our results provide high-resolution molecular information on humoral immune responses after HuNoV vaccination and demonstrate that infection-derived and vaccine-elicited antibodies can exhibit broad blockade and neutralization against this prevalent human pathogen. PubMed: 31216462DOI: 10.1016/j.immuni.2019.05.007 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.579 Å) |
Structure validation
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