Abstract
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 invitro. The structure of the NPBP/δNP<inf>NTD</inf> complex, solved to3.7Å 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 376-389 |
| Number of pages | 14 |
| Journal | Cell Reports |
| Volume | 11 |
| Issue number | 3 |
| DOIs | |
| State | Published - Apr 21 2015 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
An intrinsically disordered peptide from ebola virus VP35 controls viral RNA synthesis by modulating nucleoprotein-RNA interactions. / Leung, Daisy W.; Borek, Dominika; Luthra, Priya; Binning, Jennifer M.; Anantpadma, Manu; Liu, Gai; Harvey, Ian B.; Su, Zhaoming; Endlich-Frazier, Ariel; Pan, Juanli; Shabman, Reed S.; Chiu, Wah; Davey, Robert A.; Otwinowski, Zbyszek; Basler, Christopher F.; Amarasinghe, Gaya K.
In: Cell Reports, Vol. 11, No. 3, 21.04.2015, p. 376-389.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - An intrinsically disordered peptide from ebola virus VP35 controls viral RNA synthesis by modulating nucleoprotein-RNA interactions
AU - Leung, Daisy W.
AU - Borek, Dominika
AU - Luthra, Priya
AU - Binning, Jennifer M.
AU - Anantpadma, Manu
AU - Liu, Gai
AU - Harvey, Ian B.
AU - Su, Zhaoming
AU - Endlich-Frazier, Ariel
AU - Pan, Juanli
AU - Shabman, Reed S.
AU - Chiu, Wah
AU - Davey, Robert A.
AU - Otwinowski, Zbyszek
AU - Basler, Christopher F.
AU - Amarasinghe, Gaya K.
PY - 2015/4/21
Y1 - 2015/4/21
N2 - 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 invitro. The structure of the NPBP/δNPNTD complex, solved to3.7Å 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.
AB - 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 invitro. The structure of the NPBP/δNPNTD complex, solved to3.7Å 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84928208144&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2015.03.034
DO - 10.1016/j.celrep.2015.03.034
M3 - Article
C2 - 25865894
AN - SCOPUS:84928208144
VL - 11
SP - 376
EP - 389
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 3
ER -