9WAG

Yeast-expressed polio type 1 expanded virus-like particles

Summary for 9WAG

• Entry DOI: 10.2210/pdb9wag/pdb
• EMDB information: 65817
• Descriptor: Capsid protein VP1, Capsid protein VP2, Capsid protein VP3 (3 entities in total)
• Functional Keywords: poliovirus type 1, virus-like particles, expanded state, viral protein, virus like particle
• Biological source: Poliovirus 1; More
• Total number of polymer chains: 3
• Total formula weight: 90101.84

Authors

Hong, Q.,Cong, Y. (deposition date: 2025-08-12, release date: 2026-03-04, Last modification date: 2026-03-18)

Primary citation

Hong, Q.,Chen, T.,Han, W.,Wang, S.,Lian, C.,Zhang, Y.,Ruan, L.,Wang, T.,Lin, C.,Song, C.,Liu, Q.,Wang, X.,Cong, Y.,Huang, Z.
Structural insight into the assembly and D antigenicity of polio type 1 stabilized virus-like particles.
Npj Vaccines, 2026

PubMed Abstract: The inherent instability of poliovirus capsids presents a formidable challenge for developing next-generation vaccines suitable for a post-eradication world. Here, we address this by engineering a thermally stabilized virus-like particle (sVLP) derived from the poliovirus serotype 1 (PV1) Mahoney-SC7 mutant and elucidating its atomic-level structure. Produced at remarkably high yields in Pichia pastoris yeast, our engineered sVLP maintains a native, D-antigenic conformation and elicits a potent neutralizing antibody response in mice, in sharp contrast to unstable wild-type VLP (wtVLP) which adopts an expanded, non-immunogenic form. Our 2.43 Å resolution cryo-EM structure reveals precisely how seven stabilizing mutations cooperatively enhance inter-protomer contacts and rigidify surface loops to lock the particle in its immunogenic state. We further define a critical D-antigenic epitope by determining the 2.60 Å structure of the sVLP in complex with a novel D-antigen-specific, neutralizing monoclonal antibody, 3G10, elucidating the structural mechanisms of D-antigen recognition and virus neutralization by 3G10. These findings provide a definitive structural blueprint for engineering stable, immunogenic vaccines for PVs and other enteroviruses and also deliver a vital reagent for ensuring vaccine quality control.

PubMed: 41735326
DOI: 10.1038/s41541-026-01404-0

Experimental method

ELECTRON MICROSCOPY (2.95 Å)