7CVZ
Cryo-EM structure of Chikungunya virus in complex with Fab fragments of mAb CHK-263
Summary for 7CVZ
| Entry DOI | 10.2210/pdb7cvz/pdb |
| EMDB information | 30476 30477 |
| Descriptor | E1 glycoprotein, E2 glycoprotein, Capsid protein, ... (5 entities in total) |
| Functional Keywords | virus, fab, complex, virus-immune system complex, virus/immune system |
| Biological source | Chikungunya virus More |
| Total number of polymer chains | 16 |
| Total formula weight | 535853.21 |
| Authors | Zhou, Q.F.,Fox, J.M.,Earnest, J.T.,Ng, T.S.,Kim, A.S.,Fibriansah, G.,Kostyuchenko, V.A.,Shu, B.,Diamond, M.S.,Lok, S.M. (deposition date: 2020-08-27, release date: 2020-11-04, Last modification date: 2024-03-27) |
| Primary citation | Zhou, Q.F.,Fox, J.M.,Earnest, J.T.,Ng, T.S.,Kim, A.S.,Fibriansah, G.,Kostyuchenko, V.A.,Shi, J.,Shu, B.,Diamond, M.S.,Lok, S.M. Structural basis of Chikungunya virus inhibition by monoclonal antibodies. Proc.Natl.Acad.Sci.USA, 117:27637-27645, 2020 Cited by PubMed Abstract: Chikungunya virus (CHIKV) is an emerging viral pathogen that causes both acute and chronic debilitating arthritis. Here, we describe the functional and structural basis as to how two anti-CHIKV monoclonal antibodies, CHK-124 and CHK-263, potently inhibit CHIKV infection in vitro and in vivo. Our in vitro studies show that CHK-124 and CHK-263 block CHIKV at multiple stages of viral infection. CHK-124 aggregates virus particles and blocks attachment. Also, due to antibody-induced virus aggregation, fusion with endosomes and egress are inhibited. CHK-263 neutralizes CHIKV infection mainly by blocking virus attachment and fusion. To determine the structural basis of neutralization, we generated cryogenic electron microscopy reconstructions of Fab:CHIKV complexes at 4- to 5-Å resolution. CHK-124 binds to the E2 domain B and overlaps with the Mxra8 receptor-binding site. CHK-263 blocks fusion by binding an epitope that spans across E1 and E2 and locks the heterodimer together, likely preventing structural rearrangements required for fusion. These results provide structural insight as to how neutralizing antibody engagement of CHIKV inhibits different stages of the viral life cycle, which could inform vaccine and therapeutic design. PubMed: 33087569DOI: 10.1073/pnas.2008051117 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.7 Å) |
Structure validation
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