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4x52

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Revision as of 00:24, 26 January 2017

Human PARP13 (ZC3HAV1), C-Terminal PARP Domain (H810N; N830Y variant)

Structural highlights

4x52 is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	2x5y
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ZCCHV_HUMAN] Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)-specific ribonuclease PARN to remove the poly(A) tail, and the 3'-5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1), moloney and murine leukemia virus (MoMLV) and xenotropic MuLV-related virus (XMRV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. Isoform 1 is a more potent viral inhibitor than isoform 2. Isoform 2 acts as a positive regulator of DDX58/RIG-I signaling resulting in activation of the downstream effector IRF3 leading to the expression of type I IFNs and IFN stimulated genes (ISGs).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

The mammalian poly(ADP-ribose) polymerase (PARP) family are ADP-ribosyltransferases with diphtheria toxin homology (ARTD). Most members have mono-ADP-ribosyltransferase activity. PARP13/ARTD13, also called zinc finger antiviral protein (ZAP), has roles in viral immunity and microRNA mediated stress responses. PARP13 features a divergent PARP homology domain missing a PARP consensus sequence motif; the domain has enigmatic functions and apparently lacks catalytic activity. We used X-ray crystallography, molecular dynamics simulations and biochemical analyses to investigate the structural requirements for ADP-ribosyltransferase activity in human PARP13 and two of its functional partners in stress granules, PARP12/ARTD12, and PARP15/ BAL3/ARTD7. The crystal structure of the PARP homology domain of PARP13 shows obstruction of the canonical active site, precluding NAD+ binding. Molecular dynamics simulations indicate that this closed cleft conformation is maintained in solution. Introducing consensus side chains in PARP13 did not result in 3-aminobenzamide binding, but in further closure of the site. Three-dimensional alignment of the PARP homology domains of PARP13, PARP12, and PARP15 illustrates placement of PARP13 residues that deviate from the PARP family consensus. Introducing either one of two of these side chains into the corresponding positions in PARP15 abolished PARP15 ADP-ribosyltransferase activity. Taken together, our results show that PARP13 lacks the structural requirements for ADP-ribosyltransferase activity.

Structural Basis for Lack of ADP-Ribosyltransferase Activity in Poly(ADP-Ribose) Polymerase-13/Zinc Finger Antiviral Protein.,Karlberg T, Klepsch M, Thorsell AG, Andersson CD, Linusson A, Schuler H J Biol Chem. 2015 Jan 29. pii: jbc.M114.630160. PMID:25635049^[5]

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

References

↑ Kerns JA, Emerman M, Malik HS. Positive selection and increased antiviral activity associated with the PARP-containing isoform of human zinc-finger antiviral protein. PLoS Genet. 2008 Jan;4(1):e21. doi: 10.1371/journal.pgen.0040021. PMID:18225958 doi:http://dx.doi.org/10.1371/journal.pgen.0040021
↑ Hayakawa S, Shiratori S, Yamato H, Kameyama T, Kitatsuji C, Kashigi F, Goto S, Kameoka S, Fujikura D, Yamada T, Mizutani T, Kazumata M, Sato M, Tanaka J, Asaka M, Ohba Y, Miyazaki T, Imamura M, Takaoka A. ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses. Nat Immunol. 2011 Jan;12(1):37-44. doi: 10.1038/ni.1963. Epub 2010 Nov 21. PMID:21102435 doi:http://dx.doi.org/10.1038/ni.1963
↑ Zhu Y, Chen G, Lv F, Wang X, Ji X, Xu Y, Sun J, Wu L, Zheng YT, Gao G. Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting multiply spliced viral mRNAs for degradation. Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):15834-9. doi:, 10.1073/pnas.1101676108. Epub 2011 Aug 29. PMID:21876179 doi:http://dx.doi.org/10.1073/pnas.1101676108
↑ Wang X, Tu F, Zhu Y, Gao G. Zinc-finger antiviral protein inhibits XMRV infection. PLoS One. 2012;7(6):e39159. doi: 10.1371/journal.pone.0039159. Epub 2012 Jun 15. PMID:22720057 doi:http://dx.doi.org/10.1371/journal.pone.0039159
↑ Karlberg T, Klepsch M, Thorsell AG, Andersson CD, Linusson A, Schuler H. Structural Basis for Lack of ADP-Ribosyltransferase Activity in Poly(ADP-Ribose) Polymerase-13/Zinc Finger Antiviral Protein. J Biol Chem. 2015 Jan 29. pii: jbc.M114.630160. PMID:25635049 doi:http://dx.doi.org/10.1074/jbc.M114.630160

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/4x52"

@@ Line 1: / Line 1: @@
 ==Human PARP13 (ZC3HAV1), C-Terminal PARP Domain (H810N; N830Y variant)==
 <StructureSection load='4x52' size='340' side='right' caption='[[4x52]], [[Resolution|resolution]] 2.08&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2x5y|2x5y]]</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=4x52 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x52 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4x52 RCSB], [http://www.ebi.ac.uk/pdbsum/4x52 PDBsum]</span></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=4x52 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x52 OCA], [http://pdbe.org/4x52 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x52 RCSB], [http://www.ebi.ac.uk/pdbsum/4x52 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x52 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4x52" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4x52

From Proteopedia

Revision as of 00:24, 26 January 2017

Human PARP13 (ZC3HAV1), C-Terminal PARP Domain (H810N; N830Y variant)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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