3L27

Crystal structure of Zaire Ebola VP35 interferon inhibitory domain R312A mutant

Summary for 3L27

• Entry DOI: 10.2210/pdb3l27/pdb
• Related: 3FKE 3L25 3L26 3L28 3L29 3L2A
• Descriptor: Polymerase cofactor VP35, CHLORIDE ION, PHOSPHATE ION, ... (7 entities in total)
• Functional Keywords: rna binding domain, interferon antiviral evasion, rna replication, rna-binding protein, transcription, host cytoplasm, interferon antiviral system evasion, rna-binding, virion, rna binding protein
• Biological source: Zaire ebolavirus (ZEBOV)
• Cellular location: Virion: Q05127
• Total number of polymer chains: 4
• Total formula weight: 58587.22

Authors

Leung, D.W.,Prins, K.C.,Borek, D.M.,Farahbakhsh, M.,Tufariello, J.M.,Ramanan, P.,Nix, J.C.,Helgeson, L.A.,Otwinowski, Z.,Honzatko, R.B.,Basler, C.F.,Amarasinghe, G.K. (deposition date: 2009-12-14, release date: 2010-01-26, Last modification date: 2023-09-06)

Primary citation

Leung, D.W.,Prins, K.C.,Borek, D.M.,Farahbakhsh, M.,Tufariello, J.M.,Ramanan, P.,Nix, J.C.,Helgeson, L.A.,Otwinowski, Z.,Honzatko, R.B.,Basler, C.F.,Amarasinghe, G.K.
Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35.
Nat.Struct.Mol.Biol., 17:165-172, 2010

PubMed Abstract: 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.

PubMed: 20081868
DOI: 10.1038/nsmb.1765

Experimental method

X-RAY DIFFRACTION (1.95 Å)