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TitleAn Intrinsically Disordered Peptide from Ebola Virus VP35 Controls Viral RNA Synthesis by Modulating Nucleoprotein-RNA Interactions.
Journal, issue, pagesCell Rep, Vol. 11, Issue 3, Page 376-389, Year 2015
Publish dateApr 21, 2015
AuthorsDaisy W Leung / Dominika Borek / Priya Luthra / Jennifer M Binning / Manu Anantpadma / Gai Liu / Ian B Harvey / Zhaoming Su / Ariel Endlich-Frazier / Juanli Pan / Reed S Shabman / Wah Chiu / Robert A Davey / Zbyszek Otwinowski / Christopher F Basler / Gaya K Amarasinghe /
PubMed AbstractDuring viral RNA synthesis, Ebola virus (EBOV) nucleoprotein (NP) alternates between an RNA-template-bound form and a template-free form to provide the viral polymerase access to the RNA template. In ...During viral RNA synthesis, Ebola virus (EBOV) nucleoprotein (NP) alternates between an RNA-template-bound form and a template-free form to provide the viral polymerase access to the RNA template. In addition, newly synthesized NP must be prevented from indiscriminately binding to noncognate RNAs. Here, we investigate the molecular bases for these critical processes. We identify an intrinsically disordered peptide derived from EBOV VP35 (NPBP, residues 20-48) that binds NP with high affinity and specificity, inhibits NP oligomerization, and releases RNA from NP-RNA complexes in vitro. The structure of the NPBP/ΔNPNTD complex, solved to 3.7 Å resolution, reveals how NPBP peptide occludes a large surface area that is important for NP-NP and NP-RNA interactions and for viral RNA synthesis. Together, our results identify a highly conserved viral interface that is important for EBOV replication and can be targeted for therapeutic development.
External linksCell Rep / PubMed:25865894 / PubMed Central
MethodsX-ray diffraction
Resolution3.71 Å
Structure data

PDB-4ypi:
Structure of Ebola virus nucleoprotein N-terminal fragment bound to a peptide derived from Ebola VP35
Method: X-RAY DIFFRACTION / Resolution: 3.71 Å

Source
  • zaire ebolavirus (strain mayinga-76)
KeywordsRNA BINDING PROTEIN / protein complex. / Ebola virus / nucleoprotein / VP35 / Structural Genomics / Center for Structural Genomics of Infectious Diseases / CSGID

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