4IJE: Crystal structure of the Zaire ebolavirus VP35 interferon inhibitory domain R312A/K319A/R322A mutant

Citation:
Abstract
Viral protein 35 (VP35), encoded by filoviruses, is a multifunctional dsRNA binding protein that plays important roles in viral replication, innate immune evasion, and pathogenesis. The multifunctional nature of these proteins also presents opportunities to develop countermeasures that target distinct functional regions. However, functional validation and the establishment of therapeutic approaches toward such multifunctional proteins, particularly for nonenzymatic targets, are often challenging. Our previous work on filoviral VP35 proteins defined conserved basic residues located within its C-terminal dsRNA binding interferon (IFN) inhibitory domain (IID) as important for VP35 mediated IFN antagonism and viral polymerase cofactor functions. In the current study, we used a combination of structural and functional data to determine regions of Ebola virus (EBOV) VP35 (eVP35) to target for aptamer selection using SELEX. Select aptamers, representing, two distinct classes, were further characterized based on their interaction properties to eVP35 IID. These results revealed that these aptamers bind to distinct regions of eVP35 IID with high affinity (10-50 nM) and specificity. These aptamers can compete with dsRNA for binding to eVP35 and disrupt the eVP35-nucleoprotein (NP) interaction. Consistent with the ability to antagonize the eVP35-NP interaction, select aptamers can inhibit the function of the EBOV polymerase complex reconstituted by the expression of select viral proteins. Taken together, our results support the identification of two aptamers that bind filoviral VP35 proteins with high affinity and specificity and have the capacity to potentially function as filoviral VP35 protein inhibitors.
PDB ID: 4IJEDownload
MMDB ID: 114317
PDB Deposition Date: 2012/12/21
Updated in MMDB: 2013/12
Experimental Method:
x-ray diffraction
Resolution: 1.899  Å
Source Organism:
Similar Structures:
Biological Unit for 4IJE: monomeric; determined by author
Molecular Components in 4IJE
Label Count Molecule
Protein (1 molecule)
1
Polymerase Cofactor Vp35(Gene symbol: VP35)
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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