3l25

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of Zaire Ebola VP35 interferon inhibitory domain bound to 8 bp dsRNA

Structural highlights

3l25 is a 6 chain structure with sequence from Ebola virus - Mayinga, Zaire, 1976. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Ligands:	, , , ,
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]

Publication Abstract from PubMed

Ebola viral protein 35 (VP35), encoded by the highly pathogenic Ebola virus, facilitates host immune evasion by antagonizing antiviral signaling pathways, including those initiated by RIG-I-like receptors. Here we report the crystal structure of the Ebola VP35 interferon inhibitory domain (IID) bound to short double-stranded RNA (dsRNA), which together with in vivo results reveals how VP35-dsRNA interactions contribute to immune evasion. Conserved basic residues in VP35 IID recognize the dsRNA backbone, whereas the dsRNA blunt ends are 'end-capped' by a pocket of hydrophobic residues that mimic RIG-I-like receptor recognition of blunt-end dsRNA. Residues critical for RNA binding are also important for interferon inhibition in vivo but not for viral polymerase cofactor function of VP35. These results suggest that simultaneous recognition of dsRNA backbone and blunt ends provides a mechanism by which Ebola VP35 antagonizes host dsRNA sensors and immune responses.

Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35.,Leung DW, Prins KC, Borek DM, Farahbakhsh M, Tufariello JM, Ramanan P, Nix JC, Helgeson LA, Otwinowski Z, Honzatko RB, Basler CF, Amarasinghe GK Nat Struct Mol Biol. 2010 Feb;17(2):165-72. Epub 2010 Jan 17. PMID:20081868^[6]

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

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ Leung DW, Prins KC, Borek DM, Farahbakhsh M, Tufariello JM, Ramanan P, Nix JC, Helgeson LA, Otwinowski Z, Honzatko RB, Basler CF, Amarasinghe GK. Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35. Nat Struct Mol Biol. 2010 Feb;17(2):165-72. Epub 2010 Jan 17. PMID:20081868 doi:10.1038/nsmb.1765

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3l25"

@@ Line 1: / Line 1: @@
-{{Seed}}
-[[Image:3l25.jpg|left|200px]]
-<!--
+==Crystal structure of Zaire Ebola VP35 interferon inhibitory domain bound to 8 bp dsRNA==
-The line below this paragraph, containing "STRUCTURE_3l25", creates the "Structure Box" on the page.
+<StructureSection load='3l25' size='340' side='right'caption='[[3l25]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3l25]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Ebola_virus_-_Mayinga,_Zaire,_1976 Ebola virus - Mayinga, Zaire, 1976]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3L25 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3L25 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-{{STRUCTURE_3l25|  PDB=3l25  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3l25 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l25 OCA], [https://pdbe.org/3l25 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3l25 RCSB], [https://www.ebi.ac.uk/pdbsum/3l25 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3l25 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Ebola viral protein 35 (VP35), encoded by the highly pathogenic Ebola virus, facilitates host immune evasion by antagonizing antiviral signaling pathways, including those initiated by RIG-I-like receptors. Here we report the crystal structure of the Ebola VP35 interferon inhibitory domain (IID) bound to short double-stranded RNA (dsRNA), which together with in vivo results reveals how VP35-dsRNA interactions contribute to immune evasion. Conserved basic residues in VP35 IID recognize the dsRNA backbone, whereas the dsRNA blunt ends are 'end-capped' by a pocket of hydrophobic residues that mimic RIG-I-like receptor recognition of blunt-end dsRNA. Residues critical for RNA binding are also important for interferon inhibition in vivo but not for viral polymerase cofactor function of VP35. These results suggest that simultaneous recognition of dsRNA backbone and blunt ends provides a mechanism by which Ebola VP35 antagonizes host dsRNA sensors and immune responses.
-===Crystal structure of Zaire Ebola VP35 interferon inhibitory domain bound to 8 bp dsRNA===
+Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35.,Leung DW, Prins KC, Borek DM, Farahbakhsh M, Tufariello JM, Ramanan P, Nix JC, Helgeson LA, Otwinowski Z, Honzatko RB, Basler CF, Amarasinghe GK Nat Struct Mol Biol. 2010 Feb;17(2):165-72. Epub 2010 Jan 17. PMID:20081868<ref>PMID:20081868</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-==About this Structure==
+</div>
-L25 is a 6 chains structure with sequences 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=3L25 OCA].
+<div class="pdbe-citations 3l25" style="background-color:#fffaf0;"></div>
-[[Category: Zaire ebolavirus]]
+== References ==
-[[Category: Amarasinghe, G K.]]
+<references/>
-[[Category: Basler, C F.]]
+__TOC__
-[[Category: Borek, D M.]]
+</StructureSection>
-[[Category: Farahbakhsh, M.]]
+[[Category: Ebola virus - Mayinga, Zaire, 1976]]
-[[Category: Helgeson, L A.]]
+[[Category: Large Structures]]
-[[Category: Honzatko, R B.]]
+[[Category: Amarasinghe GK]]
-[[Category: Leung, D W.]]
+[[Category: Basler CF]]
-[[Category: Nix, J C.]]
+[[Category: Borek DM]]
-[[Category: Otwinowski, Z.]]
+[[Category: Farahbakhsh M]]
-[[Category: Prins, K C.]]
+[[Category: Helgeson LA]]
-[[Category: Ramanan, P.]]
+[[Category: Honzatko RB]]
-[[Category: Tufariello, J M.]]
+[[Category: Leung DW]]
-[[Category: Coiled coil]]
+[[Category: Nix JC]]
-[[Category: Host cytoplasm]]
+[[Category: Otwinowski Z]]
-[[Category: Interferon antiviral system evasion]]
+[[Category: Prins KC]]
-[[Category: Rna binding domain]]
+[[Category: Ramanan P]]
-[[Category: Rna binding protein]]
+[[Category: Tufariello JM]]
-[[Category: Rna replication]]
-[[Category: Rna-binding]]
-[[Category: Transcription]]
-[[Category: Virion]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 27 20:06:17 2010''

3l25

From Proteopedia

Current revision

Crystal structure of Zaire Ebola VP35 interferon inhibitory domain bound to 8 bp dsRNA

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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