8DUN
Cryo-EM Structure of Antibody SKW11 in complex with Western Equine Encephalitis Virus spike (local refinement from VLP particles)
Summary for 8DUN
| Entry DOI | 10.2210/pdb8dun/pdb |
| EMDB information | 27723 |
| Descriptor | Antibody SKW11 heavy chain, Antibody SKW11 light chain, Spike glycoprotein E1, ... (6 entities in total) |
| Functional Keywords | antibody, skw11, western equine encephalitis virus, broadly neutralizing, immune system |
| Biological source | Macaca fascicularis More |
| Total number of polymer chains | 12 |
| Total formula weight | 441076.92 |
| Authors | Cerutti, G.,Verardi, R.,Roederer, M.,Shapiro, L. (deposition date: 2022-07-27, release date: 2023-07-05, Last modification date: 2025-05-28) |
| Primary citation | Sutton, M.S.,Pletnev, S.,Callahan, V.,Ko, S.,Tsybovsky, Y.,Bylund, T.,Casner, R.G.,Cerutti, G.,Gardner, C.L.,Guirguis, V.,Verardi, R.,Zhang, B.,Ambrozak, D.,Beddall, M.,Lei, H.,Yang, E.S.,Liu, T.,Henry, A.R.,Rawi, R.,Schon, A.,Schramm, C.A.,Shen, C.H.,Shi, W.,Stephens, T.,Yang, Y.,Florez, M.B.,Ledgerwood, J.E.,Burke, C.W.,Shapiro, L.,Fox, J.M.,Kwong, P.D.,Roederer, M. Vaccine elicitation and structural basis for antibody protection against alphaviruses. Cell, 186:2672-2689.e25, 2023 Cited by PubMed Abstract: Alphaviruses are RNA viruses that represent emerging public health threats. To identify protective antibodies, we immunized macaques with a mixture of western, eastern, and Venezuelan equine encephalitis virus-like particles (VLPs), a regimen that protects against aerosol challenge with all three viruses. Single- and triple-virus-specific antibodies were isolated, and we identified 21 unique binding groups. Cryo-EM structures revealed that broad VLP binding inversely correlated with sequence and conformational variability. One triple-specific antibody, SKT05, bound proximal to the fusion peptide and neutralized all three Env-pseudotyped encephalitic alphaviruses by using different symmetry elements for recognition across VLPs. Neutralization in other assays (e.g., chimeric Sindbis virus) yielded variable results. SKT05 bound backbone atoms of sequence-diverse residues, enabling broad recognition despite sequence variability; accordingly, SKT05 protected mice against Venezuelan equine encephalitis virus, chikungunya virus, and Ross River virus challenges. Thus, a single vaccine-elicited antibody can protect in vivo against a broad range of alphaviruses. PubMed: 37295404DOI: 10.1016/j.cell.2023.05.019 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (5.84 Å) |
Structure validation
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