6Z8E

Human Picobirnavirus Ht-CP VLP

Summary for 6Z8E

• Entry DOI: 10.2210/pdb6z8e/pdb
• EMDB information: 11116
• Descriptor: Capsid protein precursor (1 entity in total)
• Functional Keywords: human picobirnavirus, cryoem, assembly, capsid protein, virus like particle
• Biological source: Human picobirnavirus
• Total number of polymer chains: 2
• Total formula weight: 132447.41

Authors

Ortega-Esteban, A.,Mata, C.P.,Rodriguez-Espinosa, M.J.,Luque, D.,Irigoyen, N.,Rodriguez, J.M.,de Pablo, P.J.,Caston, J.R. (deposition date: 2020-06-02, release date: 2020-09-23, Last modification date: 2024-05-01)

Primary citation

Ortega-Esteban, A.,Mata, C.P.,Rodriguez-Espinosa, M.J.,Luque, D.,Irigoyen, N.,Rodriguez, J.M.,de Pablo, P.J.,Caston, J.R.
Cryo-electron Microscopy Structure, Assembly, and Mechanics Show Morphogenesis and Evolution of Human Picobirnavirus.
J.Virol., 94:-, 2020

PubMed Abstract: Despite their diversity, most double-stranded-RNA (dsRNA) viruses share a specialized T=1 capsid built from dimers of a single protein that provides a platform for genome transcription and replication. This ubiquitous capsid remains structurally undisturbed throughout the viral cycle, isolating the genome to avoid triggering host defense mechanisms. Human picobirnavirus (hPBV) is a dsRNA virus frequently associated with gastroenteritis, although its pathogenicity is yet undefined. Here, we report the cryo-electron microscopy (cryo-EM) structure of hPBV at 2.6-Å resolution. The capsid protein (CP) is arranged in a single-shelled, ∼380-Å-diameter T=1 capsid with a rough outer surface similar to that of dsRNA mycoviruses. The hPBV capsid is built of 60 quasisymmetric CP dimers (A and B) stabilized by domain swapping, and only the CP-A N-terminal basic region interacts with the packaged nucleic acids. hPBV CP has an α-helical domain with a fold similar to that of fungal partitivirus CP, with many domain insertions in its C-terminal half. In contrast to dsRNA mycoviruses, hPBV has an extracellular life cycle phase like complex reoviruses, which indicates that its own CP probably participates in cell entry. Using an reversible assembly/disassembly system of hPBV, we isolated tetramers as possible assembly intermediates. We used atomic force microscopy to characterize the biophysical properties of hPBV capsids with different cargos (host nucleic acids or proteins) and found that the CP N-terminal segment not only is involved in nucleic acid interaction/packaging but also modulates the mechanical behavior of the capsid in conjunction with the cargo. Despite intensive study, human virus sampling is still sparse, especially for viruses that cause mild or asymptomatic disease. Human picobirnavirus (hPBV) is a double-stranded-RNA virus, broadly dispersed in the human population, but its pathogenicity is uncertain. Here, we report the hPBV structure derived from cryo-electron microscopy (cryo-EM) and reconstruction methods using three capsid protein variants (of different lengths and N-terminal amino acid compositions) that assemble as virus-like particles with distinct properties. The hPBV near-atomic structure reveals a quasisymmetric dimer as the structural subunit and tetramers as possible assembly intermediates that coassemble with nucleic acids. Our structural studies and atomic force microscopy analyses indicate that hPBV capsids are potentially excellent nanocages for gene therapy and targeted drug delivery in humans.

PubMed: 32938763
DOI: 10.1128/JVI.01542-20

Experimental method

ELECTRON MICROSCOPY (2.8 Å)