Cryo-EM structures of HBV capsids from human cells at near-atomic resolution
Date
2025-11-27
Journal Title
Journal ISSN
Volume Title
Publisher
Structure
Abstract
HBV causes chronic infections that can lead to severe liver disease, yet current treatments rarely achieve a cure. The HBV capsid is a critical therapeutic target, but structural insights have largely relied on E. coli-derived particles lacking native modifications. Here, we present near-atomic resolution cryo-electron microscopy (EM) structures of HBV capsids purified from human embryonic kidney (HEK-293T) cells, capturing authentic architecture and post-translational modifications. A hydrophobic pocket at the intradimer interface harbors lipid-like densities corresponding to stearic and palmitic acids, confirmed by gas chromatography- mass spectrometry. Molecular dynamics simulations revealed that pocket accessibility is regulated by rotamer states of Lys96, Phe97, and Gln99, supporting an induced fit model of fatty acid binding. Reduced phosphorylation and increased RNA content further modulate capsid conformation and pocket openness. These findings highlight the dynamic regulation of HBV capsid structure and provide a framework for understanding
how capsid conformational dynamics contribute to viral assembly and envelopment.
Description
This article was originally published in Structure. The version of record is available at: https://doi.org/10.1016/j.str.2025.11.005
© 2025 The Author(s). Published by Elsevier Inc.
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords
hepatitis B virus, capsid protein, cryo-EM, single particle analysis, molecular dynamics simulations, capsid assembly, empty capsid, hydrophobic pocket, pocket factor, fatty acid
Citation
"Bianchini, E. N., Pérez-Segura, C., Liu, H., Luckenbaugh, L., Flanagan, J., Cai, Y., Shanklin, J., Zlotnick, A., Hadden-Perilla, J. A., Hu, J., & C.-Y. Wang, J. (n.d.). Cryo-EM structures of HBV capsids from human cells at near-atomic resolution. Structure. https://doi.org/10.1016/j.str.2025.11.005 "