9AY1
Cryo-EM structure of SINV/EEEV in complex with a potently neutralizing human antibody IgG EEEV-373
Summary for 9AY1
| Entry DOI | 10.2210/pdb9ay1/pdb |
| EMDB information | 43980 |
| Descriptor | IgG EEEV-373 Heavy chain, IgG EEEV-373 Light chain, Spike glycoprotein E1, ... (8 entities in total) |
| Functional Keywords | cryo-em, single particle, virus neutralization, intra-virion crosslink, virus-immune system complex, virus |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 10 |
| Total formula weight | 377128.77 |
| Authors | Bandyopadhyay, A.,Klose, T.,Kuhn, R.J. (deposition date: 2024-03-07, release date: 2025-06-11, Last modification date: 2025-12-24) |
| Primary citation | Bandyopadhyay, A.,Williamson, L.E.,Sirohi, D.,Bailey, K.,Gilliland Jr., T.,Klose, T.,Buda, G.,Trivette, A.,Sun, C.,Julander, J.G.,Klimstra, W.B.,Crowe Jr., J.E.,Kuhn, R.J. Structural elucidation of a unique binding mode by an intact alphavirus human IgG molecule to a quaternary epitope. Nat Commun, 16:7716-7716, 2025 Cited by PubMed Abstract: Eastern equine encephalitis virus (EEEV) is a mosquito-transmitted alphavirus that can cause severe encephalitis in humans and horses with a high case fatality rate. There are no licensed EEEV vaccines or therapeutics for human use, warranting the need to better understand the human immune response against EEEV. Here we present a cryo-EM reconstruction of the chimeric virus, Sindbis (SINV)/EEEV, in complex with a potently neutralizing and efficacious intact human IgG1 antibody in a mouse model of infection and disease. This antibody requires bivalency to recognize a quaternary epitope on the E2 glycoprotein and cross-links two virus spikes across the icosahedral two-fold axis through a unique binding mode. Kinetic analysis of the binding interaction provides insights into this distinguishing feature. Mechanistically, the antibody inhibits viral entry into cells through blockade of receptor binding and early fusion events but does not block egress, thereby, exclusively targeting an epitope found on intact virions. The discovery of the quaternary epitope and unique binding mode recognized by this antibody together advance our understanding of the complexity of antibody-antigen interactions and can aid in vaccine design to elicit recognition of distinct epitopes of clinically relevant alphaviruses. PubMed: 40830099DOI: 10.1038/s41467-025-60505-x PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.6 Å) |
Structure validation
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