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Ebola virus VP30 and nucleoprotein interactions modulate viral RNA synthesis

SEbola virus VP30 and nucleoprotein interactions modulate viral RNA synthesis

Ebola virus (EBOV) is an enveloped negative-sense RNA virus that causes sporadic outbreaks with high case fatality rates. Ebola viral protein 30 (eVP30) plays a critical role in EBOV transcription initiation at the nucleoprotein (eNP) gene, with additional roles in the replication cycle such as viral assembly. However, the mechanistic basis for how eVP30 functions during the virus replication cycle is currently unclear. Here we define a key interaction between eVP30 and a peptide derived from eNP that is important to facilitate interactions leading to the recognition of the RNA template. We present crystal structures of the eVP30 C-terminus in complex with this eNP peptide. Functional analyses of the eVP30–eNP interface identify residues that are critical for viral RNA synthesis. Altogether, these results support a model where the eVP30–eNP interaction plays a critical role in transcription initiation and provides a novel target for the development of antiviral therapy.

Nat Commun. 2017 Jun 8;8:15576.
doi: 10.1038/ncomms15576.

 

© Macmillan Publishers Limited.

  Xu W, Luthra P, Wu C, Batra J, Leung DW, Basler CF, Amarasinghe GK.

Further Back:

A novel signal transduction protein: Combination of solute binding and tandem PAS-like sensor domains in one polypeptide chain
A novel signal transduction protein: Combination of solute binding and tandem PAS-like sensor domains in one polypeptide chain

 

Protein Sci. 2017 Apr;26(4):857-869.
doi: 10.1002/pro.3134.
Epub 2017 Mar 6.

Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state
Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state

 

Nat Commun. 2017 Feb 13;8:14158.
doi: 10.1038/ncomms14158.

Inhibition of RAS function through targeting an allosteric regulatory site
Inhibition of RAS function through targeting an allosteric regulatory site

 

Nat Chem Biol. 2017 Jan;13(1):62-68.
doi: 10.1038/nchembio.2231. Epub 2016 Nov 7.

Structural Basis for Ligand Binding to the Guanidine-I Riboswitch
Structural Basis for Ligand Binding to the Guanidine-I Riboswitch

 

Structure. 2017 Jan 3;25(1):195-202.
doi: 10.1016/j.str.2016.11.020.
Epub 2016 Dec 22.

 

Structural Basis of Mycobacterium tuberculosis Transcription and Transcription Inhibition

Structural Basis of Mycobacterium tuberculosis Transcription and Transcription Inhibition

 

Mol Cell. 2017 Apr 20;66(2):169-179.e8.
doi: 10.1016/j.molcel.2017.03.001.
Epub 2017 Apr 6.

A Sensitive in Vitro High-Throughput Screen To Identify Pan-filoviral Replication Inhibitors Targeting the VP35−NP Interface

A Sensitive in Vitro High-Throughput Screen To Identify Pan-filoviral Replication Inhibitors Targeting the VP35−NP Interface

 

ACS Infect Dis. 2017 Mar 10;3(3):190-198.
doi: 10.1021/acsinfecdis.6b00209.
Epub 2017 Feb 9.

Structure of the active form of human origin recognition complex and its ATPase motor module
Structure of the active form of human origin recognition complex and its ATPase motor module

 

Elife. 2017 Jan 23;6. pii: e20818.
doi: 10.7554/eLife.20818.

Non-classical transpeptidases yield insight into new antibacterials
Non-classical transpeptidases yield insight into new antibacterials

 

Nat Chem Biol. 2017 Jan;13(1):54-61.
doi: 10.1038/nchembio.2237. Epub 2016 Nov 7.

And Even Further Back:

Sidebar_2016_01
2016

 

NPAS1-ARNT and NPAS3-ARNT crystal structures implicate the bHLH-PAS family as multi-ligand binding transcription factors.

 

Bile salt receptor complex activates a pathogenic type III secretion system.

 

Crystal Structure of the FERM-SH2 Module of Human Jak2.

 

Structural Studies of Medicago truncatula Histidinol Phosphate Phosphatase from Inositol Monophosphatase Superfamily Reveal Details of Penultimate Step of Histidine Biosynthesis in Plant.

 

Crystal structure of the human sterol transporter ABCG5/ABCG8.

 

Structural basis of cohesin cleavage by separase.

 

Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana.

 

Structural and molecular basis for Ebola virus neutralization by protective human antibodies.

Sidebar_2015_01
2015

 

A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria

 

Structural basis of histone H3K27 trimethylation by an active polycomb repressive complex 2

 

A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism

 

EsxB, a secreted protein from Bacillus anthracis forms two distinct helical bundles

 

Functional Diversity of Haloacid Dehalogenase Superfamily Phosphatases from Saccharomyces cerevisiae

 

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

 

Crystal structures of alkylperoxo and anhydride intermediates in an intradiol ring-cleaving dioxygenase

 

Sidebar_2016_02
2016

 

Crystal structures of the human elongation factor eEFSec suggest a non-canonical mechanism for selenocysteine incorporation.

 

Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase.

 

Phosphorylation of spore coat proteins by a family of atypical protein kinases.

 

The mechanism of RNA 5′ capping with NAD+, NADH and desphospho-CoA.

 

The Vaccinia Virus H3 Envelope Protein, a Major Target of Neutralizing Antibodies, Exhibits a Glycosyltransferase Fold and Binds UDP-Glucose.

 

Autopalmitoylation of TEAD proteins regulates transcriptional output of the Hippo pathway.

 

Molecular mechanism of respiratory syncytial virus fusion inhibitors.

Sidebar_2015_02
2015

 

Crystal Structure of the Zorbamycin-Binding Protein ZbmA, the Primary Self-Resistance Element in Streptomyces flavoviridis ATCC21892

 

Structural Basis of Latrophilin-FLRT-UNC5 Interaction in Cell Adhesion

 

Sperm Lysozyme-Like Protein 1 (SLLP1), an intra-acrosomal oolemmal-binding sperm protein, reveals filamentous organization in protein crystal form

 

Structural integration in hypoxia-inducible factors

 

New aminopeptidase from microbial dark matter archaeon

 

A Novel Cofactor-binding Mode in Bacterial IMP Dehydrogenases Explains Inhibitor Selectivity

 

Ebola Virus VP24 Targets a Unique NLS Binding Site on Karyopherin Alpha 5 to Selectively Compete with Nuclear Import of Phos. STAT1