OCA at 08:52, 21 February 2024

2024-02-21T08:52:32Z

← Older revision		Revision as of 08:52, 21 February 2024
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	~~'''Unreleased structure'''~~

	~~The entry~~ 8cdc is ~~ON HOLD until Paper Publication~~		==Native 3CLpro from SARS-CoV-2 at 1.54 A==
			<StructureSection load='8cdc' size='340' side='right'caption='[[8cdc]], [[Resolution\|resolution]] 1.54Å' scene=''>
	~~Authors~~: ~~Mazzei~~, L., ~~Jovanovic~~, A., ~~Acton~~, T.B., ~~Ciurli~~, S., ~~Montelione~~, G.T.		== Structural highlights ==
			<table><tr><td colspan='2'>[[8cdc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8CDC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CDC FirstGlance]. <br>
	~~Description~~: ~~Native 3CLpro~~ from ~~SARS~~-~~CoV~~-2 ~~at 1~~.~~54 A~~		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.54Å</td></tr>
	[[Category: ~~Unreleased~~ Structures]]		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8cdc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cdc OCA], [https://pdbe.org/8cdc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cdc RCSB], [https://www.ebi.ac.uk/pdbsum/8cdc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cdc ProSAT]</span></td></tr>
	[[Category: ~~Ciurli, S~~]]		</table>
	[[Category: Acton~~, T.B~~]]		== Function ==
	[[Category: ~~Montelione, G.T~~]]		[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]
	[[Category: Jovanovic, A]]		== References ==
	[[Category: Mazzei, L]]		<references/>
			__TOC__
			</StructureSection>
			[[Category: Large Structures]]
			[[Category: Severe acute respiratory syndrome coronavirus 2]]
			[[Category: Acton TB]]
			[[Category: Ciurli S]]
			[[Category: Jovanovic A]]
			[[Category: Mazzei L]]
			[[Category: Montelione GT]]

OCA at 08:30, 15 February 2023

2023-02-15T08:30:42Z

← Older revision		Revision as of 08:30, 15 February 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 8cdc is ON HOLD		The entry 8cdc is ON HOLD until Paper Publication

	Authors: Mazzei, L., Jovanovic, A., Acton, T.B., Ciurli, S., Montelione, G.T.		Authors: Mazzei, L., Jovanovic, A., Acton, T.B., Ciurli, S., Montelione, G.T.

OCA: Protected "8cdc" [edit=sysop:move=sysop]

2023-02-08T05:01:35Z

Protected "8cdc" [edit=sysop:move=sysop]

← Older revision	Revision as of 05:01, 8 February 2023
(No difference)

OCA: New page: '''Unreleased structure''' The entry 8cdc is ON HOLD Authors: Mazzei, L., Jovanovic, A., Acton, T.B., Ciurli, S., Montelione, G.T. Description: Native 3CLpro from SARS-CoV-2 at 1.54 A ...

2023-02-08T05:01:34Z

New page: '''Unreleased structure''' The entry 8cdc is ON HOLD Authors: Mazzei, L., Jovanovic, A., Acton, T.B., Ciurli, S., Montelione, G.T. Description: Native 3CLpro from SARS-CoV-2 at 1.54 A ...

New page

'''Unreleased structure'''

The entry 8cdc is ON HOLD

Authors: Mazzei, L., Jovanovic, A., Acton, T.B., Ciurli, S., Montelione, G.T.

Description: Native 3CLpro from SARS-CoV-2 at 1.54 A
[[Category: Unreleased Structures]]
[[Category: Ciurli, S]]
[[Category: Acton, T.B]]
[[Category: Montelione, G.T]]
[[Category: Jovanovic, A]]
[[Category: Mazzei, L]]

8cdc - Revision history

OCA at 08:52, 21 February 2024

OCA at 08:30, 15 February 2023

OCA: Protected "8cdc" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8cdc is ON HOLD Authors: Mazzei, L., Jovanovic, A., Acton, T.B., Ciurli, S., Montelione, G.T. Description: Native 3CLpro from SARS-CoV-2 at 1.54 A ...