OCA at 08:32, 7 December 2022

OCA — Wed, 07 Dec 2022 08:32:15 GMT

←Older revision		Revision as of 08:32, 7 December 2022
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-	====	+	==SARS-CoV-2 endoribonuclease Nsp15 bound to dsRNA==
-	<StructureSection load='7tqv' size='340' side='right'caption='[[7tqv]]' scene=''>	+	<StructureSection load='7tqv' size='340' side='right'caption='[[7tqv]], [[Resolution\|resolution]] 3.43Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7tqv]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TQV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TQV 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=7tqv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tqv OCA], [https://pdbe.org/7tqv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tqv RCSB], [https://www.ebi.ac.uk/pdbsum/7tqv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tqv ProSAT]</span></td></tr>		</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=7tqv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tqv OCA], [https://pdbe.org/7tqv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tqv RCSB], [https://www.ebi.ac.uk/pdbsum/7tqv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tqv ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[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]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Coronaviruses generate double-stranded (ds) RNA intermediates during viral replication that can activate host immune sensors. To evade activation of the host pattern recognition receptor MDA5, coronaviruses employ Nsp15, which is a uridine-specific endoribonuclease. Nsp15 is proposed to associate with the coronavirus replication-transcription complex within double-membrane vesicles to cleave these dsRNA intermediates. How Nsp15 recognizes and processes dsRNA is poorly understood because previous structural studies of Nsp15 have been limited to small single-stranded (ss) RNA substrates. Here we present cryo-EM structures of SARS-CoV-2 Nsp15 bound to a 52nt dsRNA. We observed that the Nsp15 hexamer forms a platform for engaging dsRNA across multiple protomers. The structures, along with site-directed mutagenesis and RNA cleavage assays revealed critical insight into dsRNA recognition and processing. To process dsRNA Nsp15 utilizes a base-flipping mechanism to properly orient the uridine within the active site for cleavage. Our findings show that Nsp15 is a distinctive endoribonuclease that can cleave both ss- and dsRNA effectively.
		+
		+	Flipped over U: structural basis for dsRNA cleavage by the SARS-CoV-2 endoribonuclease.,Frazier MN, Wilson IM, Krahn JM, Butay KJ, Dillard LB, Borgnia MJ, Stanley RE Nucleic Acids Res. 2022 Aug 12;50(14):8290-8301. doi: 10.1093/nar/gkac589. PMID:35801916<ref>PMID:35801916</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7tqv" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Uridylate-specific endoribonuclease\|Uridylate-specific endoribonuclease]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Severe acute respiratory syndrome coronavirus 2]]
		+	[[Category: Synthetic construct]]
		+	[[Category: Borgnia MJ]]
		+	[[Category: Butay KJ]]
		+	[[Category: Dillard LB]]
		+	[[Category: Frazier MN]]
		+	[[Category: Krahn JM]]
		+	[[Category: Stanley RE]]

OCA at 11:20, 23 March 2022

OCA — Wed, 23 Mar 2022 11:20:13 GMT

←Older revision		Revision as of 11:20, 23 March 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7tqv ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7tqv' size='340' side='right'caption='[[7tqv]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~:	+	</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=7tqv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tqv OCA], [https://pdbe.org/7tqv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tqv RCSB], [https://www.ebi.ac.uk/pdbsum/7tqv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tqv ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 06:17, 9 February 2022

OCA — Wed, 09 Feb 2022 06:17:42 GMT

←Older revision		Revision as of 06:17, 9 February 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7tqv is ON HOLD	+	The entry 7tqv is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7tqv" [edit=sysop:move=sysop]

OCA — Wed, 02 Feb 2022 05:43:27 GMT

Protected "7tqv" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:43, 2 February 2022

OCA: New page: '''Unreleased structure''' The entry 7tqv is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 02 Feb 2022 05:43:26 GMT

New page: '''Unreleased structure''' The entry 7tqv is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7tqv is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7tqv - Revision history

OCA at 08:32, 7 December 2022

OCA at 11:20, 23 March 2022

OCA at 06:17, 9 February 2022

OCA: Protected "7tqv" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7tqv is ON HOLD Authors: Description: Category: Unreleased Structures