6nrl - Revision history

OCA at 06:58, 11 October 2023

2023-10-11T06:58:33Z

←Older revision		Revision as of 06:58, 11 October 2023
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	<StructureSection load='6nrl' size='340' side='right'caption='[[6nrl]], [[Resolution\|resolution]] 3.20Å' scene=''>		<StructureSection load='6nrl' size='340' side='right'caption='[[6nrl]], [[Resolution\|resolution]] 3.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nrl]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Influenza_a_virus_~~(a/blue-winged_teal/la/~~b182~~/86(~~h4n6~~)) Influenza a virus (a/blue-winged teal/la/~~b182~~/86(~~h4n6~~))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NRL OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6NRL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nrl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/blue-winged_teal/LA/B182/86(H4N6)) Influenza A virus (A/blue-winged teal/LA/B182/86(H4N6))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NRL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NRL FirstGlance]. <br>
-	</td></tr><tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~>[[4oph\|4oph]]</td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 3.2Å</td></tr>
-	~~<tr~~ id~~='gene'><td class~~="~~sblockLbl~~">~~<b>~~[[~~Gene~~\|~~Gene:~~]]~~</b></td><td class="sblockDat">NS ([http://www~~.~~ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info~~&~~srchmode=5&id=333153 Influenza A virus (A/blue-winged teal/LA/B182/86(H4N6))])~~</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=6nrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nrl OCA], [https://pdbe.org/6nrl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nrl RCSB], [https://www.ebi.ac.uk/pdbsum/6nrl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nrl ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6nrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nrl OCA], [~~http~~://pdbe.org/6nrl PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6nrl RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6nrl PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6nrl ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/Q2Y234_9INFA Q2Y234_9INFA]] Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage and polyadenylation specificity factor/CPSF4 and the poly(A)-binding protein 2/PABPN1. In turn, unprocessed 3' end pre-mRNAs accumulate in the host nucleus and are no longer exported to the cytoplasm. Cellular protein synthesis is thereby shut off very early after virus infection. Viral protein synthesis is not affected by the inhibition of the cellular 3' end processing machinery because the poly(A) tails of viral mRNAs are produced by the viral polymerase through a stuttering mechanism.[RuleBase:RU362113][SAAS:SAAS01036581] Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated DDX58 ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by binding double-strand RNA, or by interacting directly with EIF2AK2/PKR. This function may be important at the very beginning of the infection, when NS1 is mainly present in the cytoplasm. Also binds poly(A) and U6 snRNA.[RuleBase:RU362113][SAAS:SAAS01036591]	+	[https://www.uniprot.org/uniprot/Q2Y234_9INFA Q2Y234_9INFA] Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage and polyadenylation specificity factor/CPSF4 and the poly(A)-binding protein 2/PABPN1. In turn, unprocessed 3' end pre-mRNAs accumulate in the host nucleus and are no longer exported to the cytoplasm. Cellular protein synthesis is thereby shut off very early after virus infection. Viral protein synthesis is not affected by the inhibition of the cellular 3' end processing machinery because the poly(A) tails of viral mRNAs are produced by the viral polymerase through a stuttering mechanism.[RuleBase:RU362113][SAAS:SAAS01036581] Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated DDX58 ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by binding double-strand RNA, or by interacting directly with EIF2AK2/PKR. This function may be important at the very beginning of the infection, when NS1 is mainly present in the cytoplasm. Also binds poly(A) and U6 snRNA.[RuleBase:RU362113][SAAS:SAAS01036591]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 18:
	</div>		</div>
	<div class="pdbe-citations 6nrl" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6nrl" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Nonstructural protein 3D structures\|Nonstructural protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 24:		Line 26:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Hu, L]]	+	[[Category: Hu L]]
-	[[Category: Kumar, D]]	+	[[Category: Kumar D]]
-	[[Category: Mitra, S]]	+	[[Category: Mitra S]]
-	[[Category: Prasad~~, B V.V]]~~	+	[[Category: Prasad BVV]]
-	~~[[Category: Protein]]~~	+
-	~~[[Category: Viral protein~~]]	+

OCA at 17:27, 14 August 2019

2019-08-14T17:27:12Z

←Older revision		Revision as of 17:27, 14 August 2019
Line 3:		Line 3:
	<StructureSection load='6nrl' size='340' side='right'caption='[[6nrl]], [[Resolution\|resolution]] 3.20Å' scene=''>		<StructureSection load='6nrl' size='340' side='right'caption='[[6nrl]], [[Resolution\|resolution]] 3.20Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nrl]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NRL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NRL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nrl]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus_(a/blue-winged_teal/la/b182/86(h4n6)) Influenza a virus (a/blue-winged teal/la/b182/86(h4n6))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NRL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NRL FirstGlance]. <br>
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4oph\|4oph]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4oph\|4oph]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=333153 Influenza A virus (A/blue-winged teal/LA/B182/86(H4N6))])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6nrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nrl OCA], [http://pdbe.org/6nrl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nrl RCSB], [http://www.ebi.ac.uk/pdbsum/6nrl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nrl ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6nrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nrl OCA], [http://pdbe.org/6nrl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nrl RCSB], [http://www.ebi.ac.uk/pdbsum/6nrl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nrl ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/Q2Y234_9INFA Q2Y234_9INFA]] Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage and polyadenylation specificity factor/CPSF4 and the poly(A)-binding protein 2/PABPN1. In turn, unprocessed 3' end pre-mRNAs accumulate in the host nucleus and are no longer exported to the cytoplasm. Cellular protein synthesis is thereby shut off very early after virus infection. Viral protein synthesis is not affected by the inhibition of the cellular 3' end processing machinery because the poly(A) tails of viral mRNAs are produced by the viral polymerase through a stuttering mechanism.[RuleBase:RU362113][SAAS:SAAS01036581] Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated DDX58 ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by binding double-strand RNA, or by interacting directly with EIF2AK2/PKR. This function may be important at the very beginning of the infection, when NS1 is mainly present in the cytoplasm. Also binds poly(A) and U6 snRNA.[RuleBase:RU362113][SAAS:SAAS01036591]		[[http://www.uniprot.org/uniprot/Q2Y234_9INFA Q2Y234_9INFA]] Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage and polyadenylation specificity factor/CPSF4 and the poly(A)-binding protein 2/PABPN1. In turn, unprocessed 3' end pre-mRNAs accumulate in the host nucleus and are no longer exported to the cytoplasm. Cellular protein synthesis is thereby shut off very early after virus infection. Viral protein synthesis is not affected by the inhibition of the cellular 3' end processing machinery because the poly(A) tails of viral mRNAs are produced by the viral polymerase through a stuttering mechanism.[RuleBase:RU362113][SAAS:SAAS01036581] Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated DDX58 ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by binding double-strand RNA, or by interacting directly with EIF2AK2/PKR. This function may be important at the very beginning of the infection, when NS1 is mainly present in the cytoplasm. Also binds poly(A) and U6 snRNA.[RuleBase:RU362113][SAAS:SAAS01036591]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Influenza A virus (IAV) non-structural protein 1 (NS1), a potent antagonist of host immune response, is capable of interacting with RNA and a wide range of cellular proteins. NS1 consists of an RNA-binding domain (RBD) and an effector domain (ED) separated by a flexible linker region (LR). H5N1-NS1 has a characteristic 5-residue deletion in the LR with either G (minor group) or E (major group) at the 71(st) position, and non-H5N1-NS1 contains E71 with an intact linker. Based on the orientation of ED with respect to RBD, previous crystallographic studies have shown that minor group H5N1-NS1(G71), a non-H5N1-NS1 (H6N6-NS1(E71)), and the LR-deletion mutant H6N6-NS1(Delta80-84/E71) mimicking the major group H5N1-NS1, exhibit 'open', 'semi-open', and 'closed' conformations, respectively, suggesting that NS1 exhibits strain-dependent conformational preference. Here we report the first crystal structure of a naturally occurring H5N1-NS1(E71) and show that it adopts an 'open' conformation similar to the minor group of H5N1-NS1 (H5N1-NS1(G71)). We also show that H6N6-NS1(Delta80-84/E71) under a different crystallization condition and H6N6-NS1(Delta80-84/G71) also exhibit 'open' conformations, suggesting NS1 can adopt an 'open' conformation irrespective of E or G at the 71(st) position. Our single-molecule FRET analysis to investigate the conformational preference of NS1 in solution showed that all NS1 constructs predominantly exist in 'open' conformation. Further, our co-immunoprecipitation and binding studies showed that they all bind to cellular factors with similar affinity. Taken together, our studies suggest that NS1 exhibits strain-independent structural plasticity that allows it to interact with a wide variety of cellular ligands during viral infection.IMPORTANCEIAV is responsible for several pandemics over the last century and continues to infect millions annually. The frequent rise in drug-resistant strains necessitates exploring novel targets for developing antiviral drugs that can reduce the global burden of influenza infection. Because of its critical role in the replication and pathogenesis of IAV, non-structural protein 1 (NS1) is a potential target for developing antivirals. Previous studies suggested that NS1 adopts strain-dependent 'open', 'semi-open', and 'closed' conformations. Here we show, based on three crystal structures, that NS1 irrespective of strain differences can adopt 'open' conformation. We further show that NS1 from different strains primarily exists in 'open' conformation in solution and binds to cellular proteins with similar affinity. Together, our findings suggest that conformational polymorphism facilitated by a flexible linker is intrinsic to NS1, and this may be the underlying factor allowing NS1 to bind several cellular factors during IAV replication.
		+
		+	Influenza A virus protein NS1 exhibits strain-independent conformational plasticity.,Mitra S, Kumar D, Hu L, Sankaran B, Moosa MM, Rice AP, Ferreon JC, Ferreon ACM, Prasad BVV J Virol. 2019 Aug 2. pii: JVI.00917-19. doi: 10.1128/JVI.00917-19. PMID:31375595<ref>PMID:31375595</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6nrl" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 06:22, 31 July 2019

2019-07-31T06:22:55Z

←Older revision		Revision as of 06:22, 31 July 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6nrl is ~~ON HOLD until Paper Publication~~	+	==X-ray structure of H6N6-NS1 delta(80-84) R38A K41A E71G mutant==
-		+	<StructureSection load='6nrl' size='340' side='right'caption='[[6nrl]], [[Resolution\|resolution]] 3.20Å' scene=''>
-	~~Authors~~: ~~Mitra~~, S., ~~Kumar~~, D., Hu, L., ~~Prasad~~, B.V.V.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6nrl]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NRL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NRL FirstGlance]. <br>
-	~~Description~~: X-~~ray structure~~ of ~~H6N6~~-NS1 ~~delta~~(~~80-84~~) ~~R38A K41A E71G mutant~~	+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4oph\|4oph]]</td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6nrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nrl OCA], [http://pdbe.org/6nrl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nrl RCSB], [http://www.ebi.ac.uk/pdbsum/6nrl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nrl ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/Q2Y234_9INFA Q2Y234_9INFA]] Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage and polyadenylation specificity factor/CPSF4 and the poly(A)-binding protein 2/PABPN1. In turn, unprocessed 3' end pre-mRNAs accumulate in the host nucleus and are no longer exported to the cytoplasm. Cellular protein synthesis is thereby shut off very early after virus infection. Viral protein synthesis is not affected by the inhibition of the cellular 3' end processing machinery because the poly(A) tails of viral mRNAs are produced by the viral polymerase through a stuttering mechanism.[RuleBase:RU362113][SAAS:SAAS01036581] Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated DDX58 ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by binding double-strand RNA, or by interacting directly with EIF2AK2/PKR. This function may be important at the very beginning of the infection, when NS1 is mainly present in the cytoplasm. Also binds poly(A) and U6 snRNA.[RuleBase:RU362113][SAAS:SAAS01036591]
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Hu, L]]
	[[Category: Kumar, D]]		[[Category: Kumar, D]]
-	[[Category: Hu, L]]
	[[Category: Mitra, S]]		[[Category: Mitra, S]]
-	[[Category: Prasad, B.V.V]]	+	[[Category: Prasad, B V.V]]
		+	[[Category: Protein]]
		+	[[Category: Viral protein]]

OCA at 04:10, 3 July 2019

2019-07-03T04:10:02Z

←Older revision		Revision as of 04:10, 3 July 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6nrl is ON HOLD until ~~Jul 23 2020~~	+	The entry 6nrl is ON HOLD until Paper Publication

	Authors: Mitra, S., Kumar, D., Hu, L., Prasad, B.V.V.		Authors: Mitra, S., Kumar, D., Hu, L., Prasad, B.V.V.
Line 7:		Line 7:
	Description: X-ray structure of H6N6-NS1 delta(80-84) R38A K41A E71G mutant		Description: X-ray structure of H6N6-NS1 delta(80-84) R38A K41A E71G mutant
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Hu, L]]
-	[[Category: Prasad, B.V.V]]
	[[Category: Kumar, D]]		[[Category: Kumar, D]]
		+	[[Category: Hu, L]]
	[[Category: Mitra, S]]		[[Category: Mitra, S]]
		+	[[Category: Prasad, B.V.V]]

OCA at 07:39, 13 February 2019

2019-02-13T07:39:16Z

←Older revision		Revision as of 07:39, 13 February 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6nrl is ON HOLD	+	The entry 6nrl is ON HOLD until Jul 23 2020

	Authors: Mitra, S., Kumar, D., Hu, L., Prasad, B.V.V.		Authors: Mitra, S., Kumar, D., Hu, L., Prasad, B.V.V.

-	Description: X-ray structure of H6N6-NS1 delta(80-84) ~~71G~~ mutant	+	Description: X-ray structure of H6N6-NS1 delta(80-84) R38A K41A E71G mutant
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Hu, L]]		[[Category: Hu, L]]

OCA: Protected "6nrl" [edit=sysop:move=sysop]

2019-01-30T06:49:12Z

Protected "6nrl" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:49, 30 January 2019

OCA: New page: '''Unreleased structure''' The entry 6nrl is ON HOLD Authors: Mitra, S., Kumar, D., Hu, L., Prasad, B.V.V. Description: X-ray structure of H6N6-NS1 delta(80-84) 71G mutant [[Category: ...

2019-01-30T06:49:11Z

New page: '''Unreleased structure''' The entry 6nrl is ON HOLD Authors: Mitra, S., Kumar, D., Hu, L., Prasad, B.V.V. Description: X-ray structure of H6N6-NS1 delta(80-84) 71G mutant [[Category: ...

New page

'''Unreleased structure'''

The entry 6nrl is ON HOLD

Authors: Mitra, S., Kumar, D., Hu, L., Prasad, B.V.V.

Description: X-ray structure of H6N6-NS1 delta(80-84) 71G mutant
[[Category: Unreleased Structures]]
[[Category: Hu, L]]
[[Category: Prasad, B.V.V]]
[[Category: Kumar, D]]
[[Category: Mitra, S]]