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An Intrinsically Disordered Peptide from Ebola Virus VP35 Controls Viral RNA Synthesis by Modulating Nucleoprotein-RNA Interactions

Figure_3ad 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 non-cognate 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/Δ NPNTD  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.

Cell Reports. 2015, Apr 21;11(3):376–389.

Daisy 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, and Gaya K. Amarasinghe.

ANL Feature Story:

Argonne Researchers Uncover Structure of Protein Implicated in Diabetes

Hepatocyte nuclear factor 4α (HNF-4α), plays a critical role by binding to specific DNA sequences and regulating the production of a number of key proteins for normal cellular processes. Some of its mutations have been linked to maturity-onset diabetes, kidney failure and metabolic syndrome.


Nature. 2013;495(7441):394–395



12th International Conference on Synchrotron Radiation Instrumentation (SRI 2015)

July 06–10 (NY Marriott Marquis; Times Square, New York)


2015 Annual Meeting of the American Crystallographic Association

July 25–29 (Sheraton Downtown Hotel; Philadelphia, PA)


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