Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35
| Autor: | Parameshwaran Ramanan, Richard B. Honzatko, JoAnn M Tufariello, Kathleen C. Prins, Dominika Borek, Christopher F. Basler, Mina Farahbakhsh, Jay C. Nix, Daisy W. Leung, Zbyszek Otwinowski, Gaya K. Amarasinghe, Luke A. Helgeson |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Models
Molecular Viral protein viruses RNA-binding protein Biology medicine.disease_cause Crystallography X-Ray Article DEAD-box RNA Helicases Structural Biology Interferon medicine Viral Regulatory and Accessory Proteins Receptors Immunologic DEAD Box Protein 58 Molecular Biology Polymerase Immune Evasion RNA Double-Stranded Ebola virus Binding Sites virus diseases RNA-Binding Proteins MDA5 Ebolavirus Virology Protein Structure Tertiary RNA silencing biology.protein Interferons medicine.drug Protein Binding |
| Popis: | Ebola viral protein 35 (VP35), encoded by the highly pathogenic Ebola virus, facilitates host immune evasion by antagonizing antiviral signaling pathways, including those initiated by RIG-I-like receptors. Here we report the crystal structure of the Ebola VP35 interferon inhibitory domain (IID) bound to short double-stranded RNA (dsRNA), which together with in vivo results reveals how VP35-dsRNA interactions contribute to immune evasion. Conserved basic residues in VP35 IID recognize the dsRNA backbone, whereas the dsRNA blunt ends are 'end-capped' by a pocket of hydrophobic residues that mimic RIG-I-like receptor recognition of blunt-end dsRNA. Residues critical for RNA binding are also important for interferon inhibition in vivo but not for viral polymerase cofactor function of VP35. These results suggest that simultaneous recognition of dsRNA backbone and blunt ends provides a mechanism by which Ebola VP35 antagonizes host dsRNA sensors and immune responses. |
| Databáze: | OpenAIRE |
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