7vb4 - Revision history

OCA at 09:16, 17 October 2024

2024-10-17T09:16:40Z

← Older revision		Revision as of 09:16, 17 October 2024
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	<StructureSection load='7vb4' size='340' side='right'caption='[[7vb4]], [[Resolution\|resolution]] 1.86Å' scene=''>		<StructureSection load='7vb4' size='340' side='right'caption='[[7vb4]], [[Resolution\|resolution]] 1.86Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>~~[[7vb4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Sindbis_virus Sindbis virus].~~ Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VB4 FirstGlance]. <br>		<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VB4 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]] 1.86Å</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]] 1.86Å</td></tr>
	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=7vb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vb4 OCA], [https://pdbe.org/7vb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vb4 RCSB], [https://www.ebi.ac.uk/pdbsum/7vb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vb4 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=7vb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vb4 OCA], [https://pdbe.org/7vb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vb4 RCSB], [https://www.ebi.ac.uk/pdbsum/7vb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vb4 ProSAT]</span></td></tr>
	</table>		</table>
	~~== Function ==~~
	[https://www.uniprot.org/uniprot/POLN_SINDV POLN_SINDV] P123 and P123' are short-lived polyproteins, accumulating during early stage of infection. P123 is directly translated from the genome, whereas P123' is a product of the cleavage of P1234. They localize the viral replication complex to the cytoplasmic surface of modified endosomes and lysosomes. By interacting with nsP4, they start viral genome replication into antigenome. After these early events, P123 and P123' are cleaved sequentially into nsP1, nsP2 and nsP3/nsP3'. This sequence of delayed processing would allow correct assembly and membrane association of the RNA polymerase complex. nsP1 is a cytoplasmic capping enzyme. This function is necessary since all viral RNAs are synthesized in the cytoplasm, and host capping enzymes are restricted to the nucleus. The enzymatic reaction involves a covalent link between 7-methyl-GMP and nsP1, whereas eukaryotic capping enzymes form a covalent complex only with GMP. nsP1 capping would consist in the following reactions: GTP is first methylated and then forms the m7GMp-nsP1 complex, from which 7-methyl-GMP complex is transferred to the mRNA to create the cap structure. Palmitoylated nsP1 is remodeling host cell cytoskeleton, and induces filopodium-like structure formation at the surface of the host cell. nsP2 has two separate domain with different biological activities. The N-terminal section is part of the RNA polymerase complex and has RNA trisphosphatase and RNA helicase activity. The C-terminal section harbors a protease that specifically cleaves and releases the four mature proteins. Also inhibits cellular transcription by inducing rapid degradation of POLR2A, a catalytic subunit of the RNAPII complex. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response. nsP3 and nsP3' are essential for minus strand and subgenomic 26S mRNA synthesis. nsP4 is an RNA dependent RNA polymerase. It replicates genomic and antigenomic RNA by recognizing replications specific signals. Transcribes also a 26S subgenomic mRNA by initiating RNA synthesis internally on antigenomic RNA. This 26S mRNA codes for structural proteins. nsP4 is a short-lived protein regulated by several ways: the opal codon readthrough and degradation by ubiquitin pathway.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Sindbis virus]]~~
	[[Category: Luo D]]		[[Category: Luo D]]
	[[Category: Tan YB]]		[[Category: Tan YB]]

OCA at 17:22, 29 November 2023

2023-11-29T17:22:35Z

← Older revision		Revision as of 17:22, 29 November 2023
Line 1:		Line 1:

	==A crystal structure of alphavirus nonstructural protein 4 (nsP4) reveals an intrinsically dynamic RNA-dependent RNA polymerase==		==A crystal structure of alphavirus nonstructural protein 4 (nsP4) reveals an intrinsically dynamic RNA-dependent RNA polymerase==
	<StructureSection load='7vb4' size='340' side='right'caption='[[7vb4]]' scene=''>		<StructureSection load='7vb4' size='340' side='right'caption='[[7vb4]], [[Resolution\|resolution]] 1.86Å' 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=7VB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VB4 FirstGlance]. <br>		<table><tr><td colspan='2'>[[7vb4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Sindbis_virus Sindbis virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VB4 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=7vb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vb4 OCA], [https://pdbe.org/7vb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vb4 RCSB], [https://www.ebi.ac.uk/pdbsum/7vb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vb4 ProSAT]</span></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]] 1.86Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=7vb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vb4 OCA], [https://pdbe.org/7vb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vb4 RCSB], [https://www.ebi.ac.uk/pdbsum/7vb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vb4 ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[https://www.uniprot.org/uniprot/POLN_SINDV POLN_SINDV] P123 and P123' are short-lived polyproteins, accumulating during early stage of infection. P123 is directly translated from the genome, whereas P123' is a product of the cleavage of P1234. They localize the viral replication complex to the cytoplasmic surface of modified endosomes and lysosomes. By interacting with nsP4, they start viral genome replication into antigenome. After these early events, P123 and P123' are cleaved sequentially into nsP1, nsP2 and nsP3/nsP3'. This sequence of delayed processing would allow correct assembly and membrane association of the RNA polymerase complex. nsP1 is a cytoplasmic capping enzyme. This function is necessary since all viral RNAs are synthesized in the cytoplasm, and host capping enzymes are restricted to the nucleus. The enzymatic reaction involves a covalent link between 7-methyl-GMP and nsP1, whereas eukaryotic capping enzymes form a covalent complex only with GMP. nsP1 capping would consist in the following reactions: GTP is first methylated and then forms the m7GMp-nsP1 complex, from which 7-methyl-GMP complex is transferred to the mRNA to create the cap structure. Palmitoylated nsP1 is remodeling host cell cytoskeleton, and induces filopodium-like structure formation at the surface of the host cell. nsP2 has two separate domain with different biological activities. The N-terminal section is part of the RNA polymerase complex and has RNA trisphosphatase and RNA helicase activity. The C-terminal section harbors a protease that specifically cleaves and releases the four mature proteins. Also inhibits cellular transcription by inducing rapid degradation of POLR2A, a catalytic subunit of the RNAPII complex. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response. nsP3 and nsP3' are essential for minus strand and subgenomic 26S mRNA synthesis. nsP4 is an RNA dependent RNA polymerase. It replicates genomic and antigenomic RNA by recognizing replications specific signals. Transcribes also a 26S subgenomic mRNA by initiating RNA synthesis internally on antigenomic RNA. This 26S mRNA codes for structural proteins. nsP4 is a short-lived protein regulated by several ways: the opal codon readthrough and degradation by ubiquitin pathway.
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Alphaviruses such as Ross River virus (RRV), chikungunya virus (CHIKV), Sindbis virus (SINV), and Venezuelan equine encephalitis virus (VEEV) are mosquito-borne pathogens that can cause arthritis or encephalitis diseases. Nonstructural protein 4 (nsP4) of alphaviruses possesses RNA-dependent RNA polymerase (RdRp) activity essential for viral RNA replication. No 3D structure has been available for nsP4 of any alphaviruses despite its importance for understanding alphaviral RNA replication and for the design of antiviral drugs. Here, we report crystal structures of the RdRp domain of nsP4 from both RRV and SINV determined at resolutions of 2.6 A and 1.9 A. The structure of the alphavirus RdRp domain appears most closely related to RdRps from pestiviruses, noroviruses, and picornaviruses. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) and nuclear magnetic resonance (NMR) methods showed that in solution, nsP4 is highly dynamic with an intrinsically disordered N-terminal domain. Both full-length nsP4 and the RdRp domain were capable to catalyze RNA polymerization. Structure-guided mutagenesis using a trans-replicase system identified nsP4 regions critical for viral RNA replication.

			Crystal structures of alphavirus nonstructural protein 4 (nsP4) reveal an intrinsically dynamic RNA-dependent RNA polymerase fold.,Tan YB, Lello LS, Liu X, Law YS, Kang C, Lescar J, Zheng J, Merits A, Luo D Nucleic Acids Res. 2022 Jan 25;50(2):1000-1016. doi: 10.1093/nar/gkab1302. PMID:35037043<ref>PMID:35037043</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7vb4" style="background-color:#fffaf0;"></div>
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
			[[Category: Sindbis virus]]
	[[Category: Luo D]]		[[Category: Luo D]]
	[[Category: Tan YB]]		[[Category: Tan YB]]

OCA at 10:19, 16 February 2022

2022-02-16T10:19:20Z

← Older revision		Revision as of 10:19, 16 February 2022
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	~~'''Unreleased structure'''~~

	~~The entry~~ 7vb4 is ~~ON HOLD until Paper Publication~~		==A crystal structure of alphavirus nonstructural protein 4 (nsP4) reveals an intrinsically dynamic RNA-dependent RNA polymerase==
			<StructureSection load='7vb4' size='340' side='right'caption='[[7vb4]]' scene=''>
	~~Authors~~:		== Structural highlights ==
			<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VB4 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=7vb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vb4 OCA], [https://pdbe.org/7vb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vb4 RCSB], [https://www.ebi.ac.uk/pdbsum/7vb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vb4 ProSAT]</span></td></tr>
	[[Category: ~~Unreleased Structures~~]]		</table>
			__TOC__
			</StructureSection>
			[[Category: Large Structures]]
			[[Category: Luo D]]
			[[Category: Tan YB]]

OCA at 12:17, 29 December 2021

2021-12-29T12:17:46Z

← Older revision		Revision as of 12:17, 29 December 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7vb4 is ON HOLD		The entry 7vb4 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7vb4" [edit=sysop:move=sysop]

2021-09-08T08:02:22Z

Protected "7vb4" [edit=sysop:move=sysop]

← Older revision	Revision as of 08:02, 8 September 2021
(No difference)

OCA: New page: '''Unreleased structure''' The entry 7vb4 is ON HOLD Authors: Description: Category: Unreleased Structures

2021-09-08T08:02:21Z

New page: '''Unreleased structure''' The entry 7vb4 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7vb4 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]