3kwg
From Proteopedia
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{{STRUCTURE_3kwg| PDB=3kwg | SCENE= }} | {{STRUCTURE_3kwg| PDB=3kwg | SCENE= }} | ||
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===X-ray structure of NS1 effector domain W187A mutant=== | ===X-ray structure of NS1 effector domain W187A mutant=== | ||
| + | {{ABSTRACT_PUBMED_19995550}} | ||
| - | + | ==Function== | |
| - | + | [[http://www.uniprot.org/uniprot/NS1_I72A2 NS1_I72A2]] Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage and polyadenylation specificity factor (CPSF4) and the poly(A)-binding protein 2 (PABPN1). This results in the accumulation of unprocessed 3' end pre-mRNAs which can't be exported from the nucleus. Cellular protein synthesis is thereby shut off very early after virus infection. Viral protein synthesis is not affected by the inhibition of the cellular 3' end processing machinery because the poly(A) tails of viral mRNAs are produced by the viral polymerase through a stuttering mechanism.<ref>PMID:9651582</ref> <ref>PMID:9560194</ref> <ref>PMID:16571812</ref> Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated DDX58 ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors like IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by binding double-strand RNA, or by interacting directly with EIF2AK2/PKR. This function may be important at the very beginning of the infection, when NS1 is mainly present in the cytoplasm. Also binds poly(A) and U6 snRNA. Suppresses the RNA silencing-based antiviral response in Drosophila cells (By similarity).<ref>PMID:9651582</ref> <ref>PMID:9560194</ref> <ref>PMID:16571812</ref> | |
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==About this Structure== | ==About this Structure== | ||
| - | + | [[3kwg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus Influenza a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KWG OCA]. | |
==Reference== | ==Reference== | ||
| - | <ref group="xtra">PMID: | + | <ref group="xtra">PMID:019995550</ref><references group="xtra"/><references/> |
[[Category: Influenza a virus]] | [[Category: Influenza a virus]] | ||
[[Category: Robertus, J D.]] | [[Category: Robertus, J D.]] | ||
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[[Category: Suppressor of rna silencing]] | [[Category: Suppressor of rna silencing]] | ||
[[Category: Viral protein]] | [[Category: Viral protein]] | ||
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| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 24 08:21:49 2010'' | ||
Revision as of 19:56, 4 April 2013
Contents |
X-ray structure of NS1 effector domain W187A mutant
Template:ABSTRACT PUBMED 19995550
Function
[NS1_I72A2] Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage and polyadenylation specificity factor (CPSF4) and the poly(A)-binding protein 2 (PABPN1). This results in the accumulation of unprocessed 3' end pre-mRNAs which can't be exported from the nucleus. Cellular protein synthesis is thereby shut off very early after virus infection. Viral protein synthesis is not affected by the inhibition of the cellular 3' end processing machinery because the poly(A) tails of viral mRNAs are produced by the viral polymerase through a stuttering mechanism.[1] [2] [3] Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated DDX58 ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors like IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by binding double-strand RNA, or by interacting directly with EIF2AK2/PKR. This function may be important at the very beginning of the infection, when NS1 is mainly present in the cytoplasm. Also binds poly(A) and U6 snRNA. Suppresses the RNA silencing-based antiviral response in Drosophila cells (By similarity).[4] [5] [6]
About this Structure
3kwg is a 2 chain structure with sequence from Influenza a virus. Full crystallographic information is available from OCA.
Reference
- Xia S, Robertus JD. X-ray structures of NS1 effector domain mutants. Arch Biochem Biophys. 2010 Feb 15;494(2):198-204. Epub 2009 Dec 6. PMID:19995550 doi:10.1016/j.abb.2009.12.008
- ↑ Nemeroff ME, Barabino SM, Li Y, Keller W, Krug RM. Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs. Mol Cell. 1998 Jun;1(7):991-1000. PMID:9651582
- ↑ Li Y, Yamakita Y, Krug RM. Regulation of a nuclear export signal by an adjacent inhibitory sequence: the effector domain of the influenza virus NS1 protein. Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4864-9. PMID:9560194
- ↑ Twu KY, Noah DL, Rao P, Kuo RL, Krug RM. The CPSF30 binding site on the NS1A protein of influenza A virus is a potential antiviral target. J Virol. 2006 Apr;80(8):3957-65. PMID:16571812 doi:10.1128/JVI.80.8.3957-3965.2006
- ↑ Nemeroff ME, Barabino SM, Li Y, Keller W, Krug RM. Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs. Mol Cell. 1998 Jun;1(7):991-1000. PMID:9651582
- ↑ Li Y, Yamakita Y, Krug RM. Regulation of a nuclear export signal by an adjacent inhibitory sequence: the effector domain of the influenza virus NS1 protein. Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4864-9. PMID:9560194
- ↑ Twu KY, Noah DL, Rao P, Kuo RL, Krug RM. The CPSF30 binding site on the NS1A protein of influenza A virus is a potential antiviral target. J Virol. 2006 Apr;80(8):3957-65. PMID:16571812 doi:10.1128/JVI.80.8.3957-3965.2006
