View source for 9wj1


==The crystal structure of PRRSV protease nsp4==
<StructureSection load='9wj1' size='340' side='right'caption='[[9wj1]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9wj1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Porcine_reproductive_and_respiratory_syndrome_virus Porcine reproductive and respiratory syndrome virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9WJ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9WJ1 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.38&#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=9wj1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9wj1 OCA], [https://pdbe.org/9wj1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9wj1 RCSB], [https://www.ebi.ac.uk/pdbsum/9wj1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9wj1 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RPOA_PRRSV RPOA_PRRSV] Contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.  Inhibits host IFN-beta production. Plays a role in the degradation of the host transcriptional activator CREBBP protein. The degradation of host CREBBP which is a key component of the IFN enhanceosome is likely responsible for the inhibition of interferon mediated by Nsp1-alpha. Also participates in the inhibition of host NF-kappa-B activation by counteracting LUBAC-dependent induction of NF-kappa-B. Reduces host NEMO ubiquitination by blocking the interaction between the two LUBAC complex components RNF31 and SHARPIN.[UniProtKB:Q04561]  Plays a role in blocking host mRNA nuclear export to the cytoplasm and subversion of host protein synthesis (By similarity). Additionally, inhibits the interferon-activated JAK/STAT signal transduction by mediating the ubiquitination and subsequent proteasomal degradation of host KPNA1 (By similarity). Repurposes the host antiviral stress granules into a proviral platform to counteract the EIF2AK2/PKR restriction, thereby regulating the host inflammatory response (PubMed:35858300).[UniProtKB:Q04561][UniProtKB:Q9WJB2]<ref>PMID:35858300</ref>   Multifunctional protein that acts as a viral protease and as a viral antagonist of host immune response. Cleaves the nsp2/nsp3 site in the viral polyprotein. Displays deubiquitinating activity that cleaves both ubiquitinated and ISGylated products and therefore inhibits ubiquitin and ISG15-dependent host innate immunity. Also deubiquitinates host NFKBIA, thereby interfering with NFKBIA degradation and impairing subsequent NF-kappa-B activation.[UniProtKB:A0MD28]  Plays a role in the inhibition of the immune response by interacting with host IFITM1. This interaction leads to the proteasomal degradation of the IFN-induced antiviral protein IFITM1.[UniProtKB:Q04561]  Cleaves the majority of cleavage sites present in the C-terminus of the polyprotein. Triggers host apoptosis through caspase-3, -8, and -9 activations. Subverts host innate immune responses through its protease activity. Targets the NF-kappa-B essential modulator NEMO and mediates its cleavage. Blocks host interferon beta induction and downstream signaling by cleaving mitochondrial MAVS, dislodging it from the mitochondria. Impairs host defense by cleaving host mRNA-decapping enzyme DCP1A to attenuate its antiviral activity.[UniProtKB:Q04561]  Plays a role in the initial induction of autophagosomes from host endoplasmic reticulum.[UniProtKB:Q04561]  Plays a role in the inhibition of host STAT3 signaling pathway by inducing the degradation of STAT3.[UniProtKB:Q04561]  Responsible for replication and transcription of the viral RNA genome.[UniProtKB:Q04561]  Displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity.[UniProtKB:Q04561]  Plays a role in viral transcription/replication and prevents the simultaneous activation of host cell dsRNA sensors, such as MDA5/IFIH1, OAS, PKR (By similarity) and NLRP3 inflammasome (By similarity). Acts by degrading the 5'-polyuridines generated during replication of the poly(A) region of viral genomic and subgenomic RNAs. Catalyzes a two-step reaction in which a 2'3'-cyclic phosphate (2'3'-cP) is first generated by 2'-O transesterification, which is then hydrolyzed to a 3'-phosphate (3'-P) (By similarity). If not degraded, poly(U) RNA would hybridize with poly(A) RNA tails and activate host dsRNA sensors (By similarity). Also plays a role in the inhibition of host type I interferon production by recruiting host OTULIN to promote removal of linear ubiquitination targeting host NEMO (By similarity).[UniProtKB:P0C6X7][UniProtKB:P19811][UniProtKB:Q04561]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Porcine reproductive and respiratory syndrome virus]]
[[Category: Wei Z]]
[[Category: Weng J]]