OCA at 07:28, 3 May 2023

OCA — Wed, 03 May 2023 07:28:12 GMT

←Older revision		Revision as of 07:28, 3 May 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 8apx is ~~ON HOLD~~ ~~until sometime~~ in the ~~future~~	+	==CryoEM structure of the Chikungunya virus nsP1 capping pores in covalent complex with a 7GMP cap structure==
		+	<StructureSection load='8apx' size='340' side='right'caption='[[8apx]], [[Resolution\|resolution]] 3.20Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8apx]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Chikungunya_virus_strain_S27-African_prototype Chikungunya virus strain S27-African prototype]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8APX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8APX FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PJ3:(2~{S})-2-azanyl-3-[1-[[(2~{R},3~{S},4~{R},5~{R})-5-(2-azanyl-7-methyl-6-oxidanylidene-1,8-dihydropurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]imidazol-4-yl]propanoic+acid'>PJ3</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8apx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8apx OCA], [https://pdbe.org/8apx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8apx RCSB], [https://www.ebi.ac.uk/pdbsum/8apx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8apx ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/POLN_CHIKS POLN_CHIKS] P123 is short-lived polyproteins, accumulating during early stage of infection. It localizes the viral replication complex to the cytoplasmic surface of modified endosomes and lysosomes. By interacting with nsP4, it starts viral genome replication into antigenome. After these early events, P123 is cleaved sequentially into nsP1, nsP2 and nsP3. This sequence of delayed processing would allow correct assembly and membrane association of the RNA polymerase complex (By similarity). 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 (By similarity). 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 (By similarity). 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 is essential for minus strand and subgenomic 26S mRNA synthesis (By similarity). 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 (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Alphaviruses are emerging positive-stranded RNA viruses which replicate and transcribe their genomes in membranous organelles formed in the cell cytoplasm. The nonstructural protein 1 (nsP1) is responsible for viral RNA capping and gates the replication organelles by assembling into monotopic membrane-associated dodecameric pores. The capping pathway is unique to Alphaviruses; beginning with the N(7) methylation of a guanosine triphosphate (GTP) molecule, followed by the covalent linkage of an m(7)GMP group to a conserved histidine in nsP1 and the transfer of this cap structure to a diphosphate RNA. Here, we provide structural snapshots of different stages of the reaction pathway showing how nsP1 pores recognize the substrates of the methyl-transfer reaction, GTP and S-adenosyl methionine (SAM), how the enzyme reaches a metastable postmethylation state with SAH and m(7)GTP in the active site, and the subsequent covalent transfer of m(7)GMP to nsP1 triggered by the presence of RNA and postdecapping reaction conformational changes inducing the opening of the pore. In addition, we biochemically characterize the capping reaction, demonstrating specificity for the RNA substrate and the reversibility of the cap transfer resulting in decapping activity and the release of reaction intermediates. Our data identify the molecular determinants allowing each pathway transition, providing an explanation for the need for the SAM methyl donor all along the pathway and clues about the conformational rearrangements associated to the enzymatic activity of nsP1. Together, our results set ground for the structural and functional understanding of alphavirus RNA-capping and the design of antivirals.

-	~~Authors: Jones~~, R., Hons, M., ~~Reguera~~, J.	+	Structural basis and dynamics of Chikungunya alphavirus RNA capping by nsP1 capping pores.,Jones R, Hons M, Rabah N, Zamarreno N, Arranz R, Reguera J Proc Natl Acad Sci U S A. 2023 Mar 21;120(12):e2213934120. doi: , 10.1073/pnas.2213934120. Epub 2023 Mar 13. PMID:36913573<ref>PMID:36913573</ref>

-	~~Description: CryoEM structure~~ of the ~~Chikungunya virus nsP1 capping pores in covalent complex with a 7GMP cap structure~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Reguera, J~~]]	+	<div class="pdbe-citations 8apx" style="background-color:#fffaf0;"></div>
-	[[Category: Hons, M]]	+	== References ==
-	[[Category: Jones, R]]	+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Chikungunya virus strain S27-African prototype]]
		+	[[Category: Large Structures]]
		+	[[Category: Hons M]]
		+	[[Category: Jones R]]
		+	[[Category: Reguera J]]

OCA at 16:37, 19 October 2022

OCA — Wed, 19 Oct 2022 16:37:02 GMT

←Older revision		Revision as of 16:37, 19 October 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8apx is ON HOLD	+	The entry 8apx is ON HOLD until sometime in the future

	Authors: Jones, R., Hons, M., Reguera, J.		Authors: Jones, R., Hons, M., Reguera, J.

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

OCA — Thu, 18 Aug 2022 03:55:46 GMT

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

←Older revision

Revision as of 03:55, 18 August 2022

OCA: New page: '''Unreleased structure''' The entry 8apx is ON HOLD Authors: Jones, R., Hons, M., Reguera, J. Description: CryoEM structure of the Chikungunya virus nsP1 capping pores in covalent com...

OCA — Thu, 18 Aug 2022 03:55:45 GMT

New page: '''Unreleased structure''' The entry 8apx is ON HOLD Authors: Jones, R., Hons, M., Reguera, J. Description: CryoEM structure of the Chikungunya virus nsP1 capping pores in covalent com...

New page

'''Unreleased structure'''

The entry 8apx is ON HOLD

Authors: Jones, R., Hons, M., Reguera, J.

Description: CryoEM structure of the Chikungunya virus nsP1 capping pores in covalent complex with a 7GMP cap structure
[[Category: Unreleased Structures]]
[[Category: Reguera, J]]
[[Category: Hons, M]]
[[Category: Jones, R]]

8apx - Revision history

OCA at 07:28, 3 May 2023

OCA at 16:37, 19 October 2022

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

OCA: New page: '''Unreleased structure''' The entry 8apx is ON HOLD Authors: Jones, R., Hons, M., Reguera, J. Description: CryoEM structure of the Chikungunya virus nsP1 capping pores in covalent com...