title: Crystal structure of the C-terminal domain of Ebola virus VP30 reveals a role in transcription and nucleocapsid association.
abstract: Transcription of the highly pathogenic Ebola virus depends on VP30, a nucleocapsid-associated Ebola virus-specific transcription factor. The transcription activator VP30 was shown to play an essential role in Ebola virus replication, most likely by stabilizing nascent mRNA. Here we present the crystal structure of the C-terminal domain (CTD) of VP30 (VP30(CTD)) at 2.0-A resolution. VP30(CTD) folds independently into a dimeric helical assembly. The VP30(CTD) dimers assemble into hexamers that are present in virions, by an oligomerization domain located in the N terminus of VP30. Mutagenesis of conserved charged amino acids on VP30(CTD) revealed that two regions, namely a basic cluster around Lys-180 and Glu-197, are required for nucleocapsid interaction. However, only mutagenesis of the basic cluster was shown to impair transcription activation, suggesting that both processes are regulated independently. The structure and the mutagenesis results reveal a potential pocket for small-molecule inhibitors that might prevent VP30 activity and thus virus propagation as it has been shown previously by peptides, which interfere with VP30 homooligomerization.
authors.affiliation: European Molecular Biology Laboratory (EMBL), 6 Rue Jules Horowitz, 38042 Grenoble, France.
authors.forename: Bettina
authors.initials: B
authors.lastname: Hartlieb
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Muziol
authors.forename: Winfried
authors.initials: W
authors.lastname: Weissenhorn
authors.forename: Stephan
authors.initials: S
authors.lastname: Becker
mesh_terms: D019943:Amino Acid Substitution; D002460:Cell Line; D018360:Crystallography, X-Ray; D019281:Dimerization; D029043:Ebolavirus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D019251:Nucleocapsid / Q000737:chemistry; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D014157:Transcription Factors; C479897:VP30 protein, ebola virus; D014764:Viral Proteins