8xab

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Current revision (10:04, 9 October 2024) (edit) (undo)
 
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8xab FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8xab OCA], [https://pdbe.org/8xab PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8xab RCSB], [https://www.ebi.ac.uk/pdbsum/8xab PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8xab ProSAT]</span></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=8xab FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8xab OCA], [https://pdbe.org/8xab PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8xab RCSB], [https://www.ebi.ac.uk/pdbsum/8xab PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8xab ProSAT]</span></td></tr>
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== Function ==
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<div style="background-color:#fffaf0;">
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[https://www.uniprot.org/uniprot/R1AB_SARS2 R1AB_SARS2] Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.[UniProtKB:P0C6X7] Inhibits host translation by interacting with the 40S ribosomal subunit. The nsp1-40S ribosome complex further induces an endonucleolytic cleavage near the 5'UTR of host mRNAs, targeting them for degradation. Viral mRNAs are not susceptible to nsp1-mediated endonucleolytic RNA cleavage thanks to the presence of a 5'-end leader sequence and are therefore protected from degradation. By suppressing host gene expression, nsp1 facilitates efficient viral gene expression in infected cells and evasion from host immune response.[UniProtKB:P0C6X7] May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2. Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses.[UniProtKB:P0C6X7] Responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Participates together with nsp4 in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF3. Prevents also host NF-kappa-B signaling.[UniProtKB:P0C6X7] Participates in the assembly of virally-induced cytoplasmic double-membrane vesicles necessary for viral replication.[UniProtKB:P0C6X7] Cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN] (PubMed:32198291). Also able to bind an ADP-ribose-1''-phosphate (ADRP).[UniProtKB:P0C6X7]<ref>PMID:32198291</ref> Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. Later, limits the expansion of these phagosomes that are no longer able to deliver viral components to lysosomes.[UniProtKB:P0C6X7] Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[UniProtKB:P0C6X7] Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers.[UniProtKB:P0C6X7] May participate in viral replication by acting as a ssRNA-binding protein.[UniProtKB:P0C6X7] Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities. Therefore plays an essential role in viral mRNAs cap methylation.[UniProtKB:P0C6X7] Responsible for replication and transcription of the viral RNA genome.[UniProtKB:P0C6X7] Multi-functional protein with a zinc-binding domain in N-terminus displaying RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Activity of helicase is dependent on magnesium.[UniProtKB:P0C6X7] Enzyme possessing two different activities: an exoribonuclease activity acting on both ssRNA and dsRNA in a 3' to 5' direction and a N7-guanine methyltransferase activity. Acts as a proofreading exoribonuclease for RNA replication, thereby lowering The sensitivity of the virus to RNA mutagens.[UniProtKB:P0C6X7] Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond.[UniProtKB:P0C6X7] Methyltransferase that mediates mRNA cap 2'-O-ribose methylation to the 5'-cap structure of viral mRNAs. N7-methyl guanosine cap is a prerequisite for binding of nsp16. Therefore plays an essential role in viral mRNAs cap methylation which is essential to evade immune system.[UniProtKB:P0C6X7]
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== Publication Abstract from PubMed ==
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The connection between SARS-CoV-2 replication-transcription complexes (RTCs) and nucleocapsid (N) protein is critical for regulating genomic RNA replication and virion packaging over the viral life cycle. However, the mechanism that dynamically regulates genomic RNA packaging and replication remains elusive. Here, we demonstrate that the N-terminal domain (NTD) of SARS-CoV-2 nonstructural protein 3 (Nsp3), a core component of viral RTCs, binds N protein and displaces RNA in a concentration-dependent manner. This interaction disrupts liquid-liquid phase separation of N protein driven by N protein-RNA interactions which is crucial for virion packaging and viral replication. We also report a high-resolution crystal structure of the Nsp3 ubiquitin-like domain 1 (Ubl1) at 1.49 A, which reveals abundant negative charges on the protein surface. Sequence and structural analyses identify several conserved motifs at the Ubl1-N protein interface and a previously unexplored highly negative groove, providing insights into the molecular mechanism of Ubl1-mediated modulation of N protein-RNA binding. Our findings elucidate the mechanism of dynamic regulation of SARS-CoV-2 genomic RNA replication and packaging over the viral life cycle. Targeting the conserved Ubl1-N protein interaction hotspots also promises to aid in the development of broad-spectrum antivirals against pathogenic coronaviruses.
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N-terminus of SARS-CoV-2 nonstructural protein 3 interrupts RNA-driven phase separation of N protein by displacing RNA.,Ke Z, Zhang H, Wang Y, Wang J, Peng F, Wang J, Liu X, Hu H, Li Y J Biol Chem. 2024 Sep 26:107828. doi: 10.1016/j.jbc.2024.107828. PMID:39341499<ref>PMID:39341499</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 8xab" style="background-color:#fffaf0;"></div>
== References ==
== References ==
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Current revision

Crystal structure of Ubl1 domain of nonstructural protein 3 of SARS-CoV-2

PDB ID 8xab

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