EMD-38166

Single-particle
2.89 Å
EMD-38166 Deposition: 29/11/2023
Map released: 04/09/2024
Last modified: 15/01/2025
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-38166

Cryo-EM structure of enterovirus A71 A-particle in complex with Fab h1A6.2

EMD-38166

Single-particle
2.89 Å
EMD-38166 Deposition: 29/11/2023
Map released: 04/09/2024
Last modified: 15/01/2025
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Enterovirus A71, Mus
Sample: Enterovirus 71 A-particle in complex with Fab h1A6.2
Fitted models: 8x96

Deposition Authors: Jiang Y , Huang Y, Zhu R , Zheng Q , Li S , Xia N
Broadly therapeutic antibody provides cross-serotype protection against enteroviruses via Fc effector functions and by mimicking SCARB2.
PUBMED: 39424982
DOI: doi:10.1038/s41564-024-01822-7
ISSN: 2058-5276
Abstract:
Enteroviruses contain multiple serotypes and can cause severe neurological complications. The intricate life cycle of enteroviruses involving dynamic virus-receptor interaction hampers the development of broad therapeutics and vaccines. Here, using function-based screening, we identify a broadly therapeutic antibody h1A6.2 that potently protects mice in lethal models of infection with both enterovirus A71 and coxsackievirus A16 through multiple mechanisms, including inhibition of the virion-SCARB2 interactions and monocyte/macrophage-dependent Fc effector functions. h1A6.2 mitigates inflammation and improves intramuscular mechanics, which are associated with diminished innate immune signalling and preserved tissue repair. Moreover, cryogenic electron microscopy structures delineate an adaptive binding of h1A6.2 to the flexible and dynamic nature of the VP2 EF loop with a binding angle mimicking the SCARB2 receptor. The coordinated binding mode results in efficient binding of h1A6.2 to all viral particle types and facilitates broad neutralization of enterovirus, therefore informing a promising target for the structure-guided design of pan-enterovirus vaccine.