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Title: An intrinsically disordered peptide from Ebola virus VP35 controls viral RNA synthesis by modulating nucleoprotein-RNA interactions

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.
 [1] ;  [2] ;  [3] ;  [1] ;  [4] ;  [1] ;  [1] ;  [5] ;  [3] ;  [1] ;  [6] ;  [5] ;  [7] ;  [2] ;  [3] ;  [1]
  1. Washington Univ. School of Medicine, St. Louis, MO (United States)
  2. Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)
  3. Icahn School of Medicine at Mount Sinai, New York, NY (United States)
  4. Texas Biomedical Research Inst., San Antonio, TX (United States)
  5. Bayor College of Medicine, Houston, TX (United States)
  6. Icahn School of Medicine at Mount Sinai, New York, NY (United States); J. Craid Venter Inst., Rockville, MD (United States)
  7. Texas Biomedical Research Inst., San Antonio, TX (United States)
Publication Date:
OSTI Identifier:
Grant/Contract Number:
Accepted Manuscript
Journal Name:
Cell Reports
Additional Journal Information:
Journal Volume: 11; Journal Issue: 3; Journal ID: ISSN 2211-1247
Research Org:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Org:
USDOE Office of Science (SC)
Country of Publication:
United States