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3f5t

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Revision as of 21:34, 2 December 2018

X-ray Structure of H5N1 NS1

Structural highlights

3f5t is a 1 chain structure with sequence from Influenza virus. This structure supersedes the now removed PDB entry 3eu6. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2gx9
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[A5A5U1_9INFA] 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.[SAAS:SAAS00141143] 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.[SAAS:SAAS00141179]

Publication Abstract from PubMed

The recent emergence of highly pathogenic avian (H5N1) influenza viruses, their epizootic and panzootic nature, and their association with lethal human infections have raised significant global health concerns. Several studies have underlined the importance of non-structural protein NS1 in the increased pathogenicity and virulence of these strains. NS1, which consists of two domains-a double-stranded RNA (dsRNA) binding domain and the effector domain, separated through a linker-is an antagonist of antiviral type-I interferon response in the host. Here we report the X-ray structure of the full-length NS1 from an H5N1 strain (A/Vietnam/1203/2004) that was associated with 60% of human deaths in an outbreak in Vietnam. Compared to the individually determined structures of the RNA binding domain and the effector domain from non-H5N1 strains, the RNA binding domain within H5N1 NS1 exhibits modest structural changes, while the H5N1 effector domain shows significant alteration, particularly in the dimeric interface. Although both domains in the full-length NS1 individually participate in dimeric interactions, an unexpected finding is that these interactions result in the formation of a chain of NS1 molecules instead of distinct dimeric units. Three such chains in the crystal interact with one another extensively to form a tubular organization of similar dimensions to that observed in the cryo-electron microscopy images of NS1 in the presence of dsRNA. The tubular oligomeric organization of NS1, in which residues implicated in dsRNA binding face a 20-A-wide central tunnel, provides a plausible mechanism for how NS1 sequesters varying lengths of dsRNA, to counter cellular antiviral dsRNA response pathways, while simultaneously interacting with other cellular ligands during an infection.

X-ray structure of NS1 from a highly pathogenic H5N1 influenza virus.,Bornholdt ZA, Prasad BV Nature. 2008 Nov 5. PMID:18987632^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bornholdt ZA, Prasad BV. X-ray structure of NS1 from a highly pathogenic H5N1 influenza virus. Nature. 2008 Nov 5. PMID:18987632 doi:nature07444

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3f5t"

@@ Line 3: / Line 3: @@
 <StructureSection load='3f5t' size='340' side='right' caption='[[3f5t]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3f5t]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Unidentified_influenza_virus Unidentified influenza virus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3eu6 3eu6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F5T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3F5T FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3f5t]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_virus Influenza virus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3eu6 3eu6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F5T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3F5T FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2gx9|2gx9]]</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3f5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f5t OCA], [http://pdbe.org/3f5t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3f5t RCSB], [http://www.ebi.ac.uk/pdbsum/3f5t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3f5t ProSAT]</span></td></tr>
@@ Line 25: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Unidentified influenza virus]]
+[[Category: Influenza virus]]
 [[Category: Bornholdt, Z A]]
 [[Category: Prasad, B V.V]]

3f5t

From Proteopedia

Revision as of 21:34, 2 December 2018

X-ray Structure of H5N1 NS1

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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