6LB0
The cryo-EM structure of HEV VLP in complex with Fab 8C11
Summary for 6LB0
| Entry DOI | 10.2210/pdb6lb0/pdb |
| EMDB information | 0866 |
| Descriptor | Protein ORF2 (1 entity in total) |
| Functional Keywords | hev, neutralizing antibody, immune-complex, virus like particle |
| Biological source | Hepatitis E virus (HEV) |
| Total number of polymer chains | 1 |
| Total formula weight | 51303.06 |
| Authors | |
| Primary citation | Zheng, Q.,Jiang, J.,He, M.,Zheng, Z.,Yu, H.,Li, T.,Xue, W.,Tang, Z.,Ying, D.,Li, Z.,Song, S.,Liu, X.,Wang, K.,Zhang, Z.,Wang, D.,Wang, Y.,Yan, X.,Zhao, Q.,Zhang, J.,Gu, Y.,Li, S.,Xia, N. Viral neutralization by antibody-imposed physical disruption. Proc.Natl.Acad.Sci.USA, 2019 Cited by PubMed Abstract: In adaptive immunity, organisms produce neutralizing antibodies (nAbs) to eliminate invading pathogens. Here, we explored whether viral neutralization could be attained through the physical disruption of a virus upon nAb binding. We report the neutralization mechanism of a potent nAb 8C11 against the hepatitis E virus (HEV), a nonenveloped positive-sense single-stranded RNA virus associated with abundant acute hepatitis. The 8C11 binding flanks the protrusion spike of the HEV viruslike particles (VLPs) and leads to tremendous physical collision between the antibody and the capsid, dissociating the VLPs into homodimer species within 2 h. Cryo-electron microscopy reconstruction of the dissociation intermediates at an earlier (15-min) stage revealed smeared protrusion spikes and a loss of icosahedral symmetry with the capsid core remaining unchanged. This structural disruption leads to the presence of only a few native HEV virions in the ultracentrifugation pellet and exposes the viral genome. Conceptually, we propose a strategy to raise collision-inducing nAbs against single spike moieties that feature in the context of the entire pathogen at positions where the neighboring space cannot afford to accommodate an antibody. This rationale may facilitate unique vaccine development and antimicrobial antibody design. PubMed: 31818956DOI: 10.1073/pnas.1916028116 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.6 Å) |
Structure validation
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