EMD-30476

Single-particle
5.2 Å
EMD-30476 Deposition: 27/08/2020
Map released: 04/11/2020
Last modified: 27/03/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-30476

Cryo-EM structure of Chikungunya virus in complex with Fab fragments of mAb CHK-124

EMD-30476

Single-particle
5.2 Å
EMD-30476 Deposition: 27/08/2020
Map released: 04/11/2020
Last modified: 27/03/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Chikungunya virus, Mus musculus
Sample: Chikungunya virus in complex with Fab fragments of mAb CHK-124
Fitted models: 7cvy (Avg. Q-score: 0.178)

Deposition Authors: Zhou QF , Fox JM , Earnest JT, Ng TS , Kim AS , Fibriansah G , Kostyuchenko VA , Shu B , Diamond MS , Lok SM
Structural basis of Chikungunya virus inhibition by monoclonal antibodies.
Zhou QF , Fox JM , Earnest JT, Ng TS , Kim AS , Fibriansah G , Kostyuchenko VA , Shi J, Shu B , Diamond MS , Lok SM
(2020) PNAS , 117 , 27637 - 27645
PUBMED: 33087569
DOI: doi:10.1073/pnas.2008051117
ISSN: 1091-6490
ASTM: PNASA6
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.