2i8b: Difference between revisions

Revision as of 18:50, 21 February 2008

Crystal structure of the C-terminal domain of Ebola virus VP30

OverviewOverview

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.

About this StructureAbout this Structure

2I8B is a Single protein structure of sequence from Zaire ebolavirus. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of the C-terminal domain of Ebola virus VP30 reveals a role in transcription and nucleocapsid association., Hartlieb B, Muziol T, Weissenhorn W, Becker S, Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):624-9. Epub 2007 Jan 3. PMID:17202263

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-[[Image:2i8b.gif|left|200px]]<br /><applet load="2i8b" size="450" color="white" frame="true" align="right" spinBox="true"
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 caption="2i8b, resolution 2.00&Aring;" />
 '''Crystal structure of the C-terminal domain of Ebola virus VP30'''<br />
 ==Overview==
-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.
+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.
 ==About this Structure==
-I8B is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Zaire_ebolavirus Zaire ebolavirus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2I8B OCA].
+I8B is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Zaire_ebolavirus Zaire ebolavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I8B OCA].
 ==Reference==
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 [[Category: Becker, S.]]
 [[Category: Hartlieb, B.]]
-[[Category: Muziol, T.M.]]
+[[Category: Muziol, T M.]]
 [[Category: Weissenhorn, W.]]
 [[Category: rna binding]]
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 [[Category: vp30 ebola virus protein]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 12:11:32 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:50:06 2008''