6Z8D

Human Picobirnavirus CP VLP

6Z8D の概要

• エントリーDOI: 10.2210/pdb6z8d/pdb
• EMDBエントリー: 11115
• 分子名称: Capsid protein precursor (1 entity in total)
• 機能のキーワード: human picobirnavirus, cryoem, assembly, capsid protein, virus like particle
• 由来する生物種: Human picobirnavirus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 124168.45

構造登録者

Ortega-Esteban, A.,Mata, C.P.,Rodriguez-Espinosa, M.J.,Luque, D.,Irigoyen, N.,Rodriguez, J.M.,de Pablo, P.J.,Caston, J.R. (登録日: 2020-06-02, 公開日: 2020-09-23, 最終更新日: 2024-05-22)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.63 Å)