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==Crystal Structure of Zaire ebolavirus VP35 RNA binding domain mutant I278A==
==Crystal Structure of Zaire ebolavirus VP35 RNA binding domain mutant I278A==
<StructureSection load='5bpv' size='340' side='right' caption='[[5bpv]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
<StructureSection load='5bpv' size='340' side='right'caption='[[5bpv]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5bpv]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BPV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BPV FirstGlance]. <br>
<table><tr><td colspan='2'>[[5bpv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Zaire_ebolavirus Zaire ebolavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BPV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BPV FirstGlance]. <br>
</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=5bpv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bpv OCA], [http://pdbe.org/5bpv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bpv RCSB], [http://www.ebi.ac.uk/pdbsum/5bpv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5bpv ProSAT]</span></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.952&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5bpv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bpv OCA], [https://pdbe.org/5bpv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bpv RCSB], [https://www.ebi.ac.uk/pdbsum/5bpv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bpv ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/VP35_EBOZ5 VP35_EBOZ5]] Acts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. This blockage is produced through the interaction with and inhibition host IKBKE and TBK1 producing a strong inhibition of the phosphorylation and activation of IRF3. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR (By similarity).  
[https://www.uniprot.org/uniprot/VP35_EBOZM VP35_EBOZM] Acsts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. The mechanism by which this blockage occurs remains incompletely defined, a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR.<ref>PMID:9971816</ref> <ref>PMID:11027311</ref> <ref>PMID:12829834</ref> <ref>PMID:16495261</ref> <ref>PMID:17065211</ref>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Alcaro, S]]
[[Category: Large Structures]]
[[Category: Bianco, G]]
[[Category: Zaire ebolavirus]]
[[Category: Cannas, V]]
[[Category: Alcaro S]]
[[Category: Corona, A]]
[[Category: Bianco G]]
[[Category: Daino, G L]]
[[Category: Cannas V]]
[[Category: Distinto, S]]
[[Category: Corona A]]
[[Category: Esposito, F]]
[[Category: Daino GL]]
[[Category: Fadda, V]]
[[Category: Distinto S]]
[[Category: Maccioni, E]]
[[Category: Esposito F]]
[[Category: Taylor, G L]]
[[Category: Fadda V]]
[[Category: Tramontano, E]]
[[Category: Maccioni E]]
[[Category: Zinzula, L]]
[[Category: Taylor GL]]
[[Category: Interferon inhibitor]]
[[Category: Tramontano E]]
[[Category: Polymerase cofactor]]
[[Category: Zinzula L]]
[[Category: Viral protein]]

Latest revision as of 14:16, 10 January 2024

Crystal Structure of Zaire ebolavirus VP35 RNA binding domain mutant I278ACrystal Structure of Zaire ebolavirus VP35 RNA binding domain mutant I278A

Structural highlights

5bpv is a 2 chain structure with sequence from Zaire ebolavirus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.952Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

VP35_EBOZM Acsts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. The mechanism by which this blockage occurs remains incompletely defined, a hypothesis suggests that VP35 dsRNA-binding activity prevents activation of IRF3 by sequestering dsRNA. Also inhibits the antiviral effect mediated by the interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR.[1] [2] [3] [4] [5]

References

  1. ↑ Muhlberger E, Weik M, Volchkov VE, Klenk HD, Becker S. Comparison of the transcription and replication strategies of marburg virus and Ebola virus by using artificial replication systems. J Virol. 1999 Mar;73(3):2333-42. PMID:9971816
  2. ↑ Basler CF, Wang X, Muhlberger E, Volchkov V, Paragas J, Klenk HD, Garcia-Sastre A, Palese P. The Ebola virus VP35 protein functions as a type I IFN antagonist. Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12289-94. PMID:11027311 doi:10.1073/pnas.220398297
  3. ↑ Basler CF, Mikulasova A, Martinez-Sobrido L, Paragas J, Muhlberger E, Bray M, Klenk HD, Palese P, Garcia-Sastre A. The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. J Virol. 2003 Jul;77(14):7945-56. PMID:12829834
  4. ↑ Enterlein S, Warfield KL, Swenson DL, Stein DA, Smith JL, Gamble CS, Kroeker AD, Iversen PL, Bavari S, Muhlberger E. VP35 knockdown inhibits Ebola virus amplification and protects against lethal infection in mice. Antimicrob Agents Chemother. 2006 Mar;50(3):984-93. PMID:16495261 doi:10.1128/AAC.50.3.984-993.2006
  5. ↑ Feng Z, Cerveny M, Yan Z, He B. The VP35 protein of Ebola virus inhibits the antiviral effect mediated by double-stranded RNA-dependent protein kinase PKR. J Virol. 2007 Jan;81(1):182-92. Epub 2006 Oct 25. PMID:17065211 doi:JVI.01006-06

5bpv, resolution 1.95Å

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