7kzh

From Proteopedia

(Difference between revisions)

Revision as of 07:44, 11 January 2023

Zinc finger antiviral protein (ZAP) central domain

Structural highlights

7kzh is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
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

Zinc-finger antiviral protein (ZAP), also known as poly(ADP-ribose) polymerase 13 (PARP13), is an antiviral factor that selectively targets viral RNA for degradation. ZAP is active against both DNA and RNA viruses, including important human pathogens such as hepatitis B virus and type 1 human immunodeficiency virus (HIV-1). ZAP selectively binds CpG dinucleotides through its N-terminal RNA-binding domain, which consists of four zinc fingers. ZAP also contains a central region that consists of a fifth zinc finger and two WWE domains. Through structural and biochemical studies, we found that the fifth zinc finger and tandem WWEs of ZAP combine into a single integrated domain that binds to poly(ADP-ribose) (PAR), a cellular polynucleotide. PAR binding is mediated by the second WWE module of ZAP and likely involves specific recognition of an adenosine diphosphate-containing unit of PAR. Mutation of the PAR binding site in ZAP abrogates the interaction in vitro and diminishes ZAP activity against a CpG-rich HIV-1 reporter virus and murine leukemia virus. In cells, PAR facilitates formation of non-membranous sub-cellular compartments such as DNA repair foci, spindle poles and cytosolic RNA stress granules. Our results suggest that ZAP-mediated viral mRNA degradation is facilitated by PAR, and provides a biophysical rationale for the reported association of ZAP with RNA stress granules.

Poly(ADP-ribose) potentiates ZAP antiviral activity.,Xue G, Braczyk K, Goncalves-Carneiro D, Dawidziak DM, Sanchez K, Ong H, Wan Y, Zadrozny KK, Ganser-Pornillos BK, Bieniasz PD, Pornillos O PLoS Pathog. 2022 Feb 7;18(2):e1009202. doi: 10.1371/journal.ppat.1009202. , eCollection 2022 Feb. PMID:35130321^[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
↑ Xue G, Braczyk K, Goncalves-Carneiro D, Dawidziak DM, Sanchez K, Ong H, Wan Y, Zadrozny KK, Ganser-Pornillos BK, Bieniasz PD, Pornillos O. Poly(ADP-ribose) potentiates ZAP antiviral activity. PLoS Pathog. 2022 Feb 7;18(2):e1009202. doi: 10.1371/journal.ppat.1009202. , eCollection 2022 Feb. PMID:35130321 doi:http://dx.doi.org/10.1371/journal.ppat.1009202

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/7kzh"

Categories: Homo sapiens | Large Structures | Pornillos OP

@@ Line 1: / Line 1: @@
 ==Zinc finger antiviral protein (ZAP) central domain==
-<StructureSection load='7kzh' size='340' side='right'caption='[[7kzh]]' scene=''>
+<StructureSection load='7kzh' size='340' side='right'caption='[[7kzh]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KZH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KZH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7kzh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KZH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KZH FirstGlance]. <br>
-</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=7kzh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kzh OCA], [https://pdbe.org/7kzh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kzh RCSB], [https://www.ebi.ac.uk/pdbsum/7kzh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kzh ProSAT]</span></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=7kzh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kzh OCA], [https://pdbe.org/7kzh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kzh RCSB], [https://www.ebi.ac.uk/pdbsum/7kzh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kzh ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/ZCCHV_HUMAN 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).<ref>PMID:18225958</ref> <ref>PMID:21102435</ref> <ref>PMID:21876179</ref> <ref>PMID:22720057</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Zinc-finger antiviral protein (ZAP), also known as poly(ADP-ribose) polymerase 13 (PARP13), is an antiviral factor that selectively targets viral RNA for degradation. ZAP is active against both DNA and RNA viruses, including important human pathogens such as hepatitis B virus and type 1 human immunodeficiency virus (HIV-1). ZAP selectively binds CpG dinucleotides through its N-terminal RNA-binding domain, which consists of four zinc fingers. ZAP also contains a central region that consists of a fifth zinc finger and two WWE domains. Through structural and biochemical studies, we found that the fifth zinc finger and tandem WWEs of ZAP combine into a single integrated domain that binds to poly(ADP-ribose) (PAR), a cellular polynucleotide. PAR binding is mediated by the second WWE module of ZAP and likely involves specific recognition of an adenosine diphosphate-containing unit of PAR. Mutation of the PAR binding site in ZAP abrogates the interaction in vitro and diminishes ZAP activity against a CpG-rich HIV-1 reporter virus and murine leukemia virus. In cells, PAR facilitates formation of non-membranous sub-cellular compartments such as DNA repair foci, spindle poles and cytosolic RNA stress granules. Our results suggest that ZAP-mediated viral mRNA degradation is facilitated by PAR, and provides a biophysical rationale for the reported association of ZAP with RNA stress granules.
+Poly(ADP-ribose) potentiates ZAP antiviral activity.,Xue G, Braczyk K, Goncalves-Carneiro D, Dawidziak DM, Sanchez K, Ong H, Wan Y, Zadrozny KK, Ganser-Pornillos BK, Bieniasz PD, Pornillos O PLoS Pathog. 2022 Feb 7;18(2):e1009202. doi: 10.1371/journal.ppat.1009202. , eCollection 2022 Feb. PMID:35130321<ref>PMID:35130321</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 7kzh" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
 [[Category: Pornillos OP]]

7kzh

From Proteopedia

Revision as of 07:44, 11 January 2023

Zinc finger antiviral protein (ZAP) central domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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