6qxe - Revision history

OCA at 05:11, 11 April 2020

OCA — Sat, 11 Apr 2020 05:11:20 GMT

←Older revision		Revision as of 05:11, 11 April 2020
Line 3:		Line 3:
	<SX load='6qxe' size='340' side='right' viewer='molstar' caption='[[6qxe]], [[Resolution\|resolution]] 4.15Å' scene=''>		<SX load='6qxe' size='340' side='right' viewer='molstar' caption='[[6qxe]], [[Resolution\|resolution]] 4.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qxe]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/I68a6 I68a6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QXE OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6QXE FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qxe]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/I68a6 I68a6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QXE OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6QXE FirstGlance]. <br>
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=P:2-DEOXY-N1,N2-PROPANO+GUANOSINE+MONOPHOSPHATE'>P</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=P:2-DEOXY-N1,N2-PROPANO+GUANOSINE+MONOPHOSPHATE'>P</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6qx3\|6qx3]], [[6qx8\|6qx8]], [[6qpg\|6qpg]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6qx3\|6qx3]], [[6qx8\|6qx8]], [[6qpg\|6qpg]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=384505 I68A6]), PB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=384505 I68A6]), PB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=384505 I68A6])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=384505 I68A6]), PB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=384505 I68A6]), PB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=384505 I68A6])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </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=6qxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qxe OCA], [http://pdbe.org/6qxe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qxe RCSB], [http://www.ebi.ac.uk/pdbsum/6qxe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qxe ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6qxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qxe OCA], [http://pdbe.org/6qxe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qxe RCSB], [http://www.ebi.ac.uk/pdbsum/6qxe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qxe ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 23:56, 6 March 2020

OCA — Fri, 06 Mar 2020 23:56:39 GMT

←Older revision		Revision as of 23:56, 6 March 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6qxe is ~~ON HOLD until Mar 07 2021~~	+	==Influenza A virus (A/NT/60/1968) polymerase dimer of hetermotrimer in complex with 3'5' cRNA promoter and Nb8205==
		+	<SX load='6qxe' size='340' side='right' viewer='molstar' caption='[[6qxe]], [[Resolution\|resolution]] 4.15Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6qxe]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/I68a6 I68a6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QXE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QXE FirstGlance]. <br>
		+	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=P:2-DEOXY-N1,N2-PROPANO+GUANOSINE+MONOPHOSPHATE'>P</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6qx3\|6qx3]], [[6qx8\|6qx8]], [[6qpg\|6qpg]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=384505 I68A6]), PB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=384505 I68A6]), PB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=384505 I68A6])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </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=6qxe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qxe OCA], [http://pdbe.org/6qxe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qxe RCSB], [http://www.ebi.ac.uk/pdbsum/6qxe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qxe ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PB2_I68A6 PB2_I68A6]] Plays an essential role in transcription initiation and cap-stealing mechanism, in which cellular capped pre-mRNAs are used to generate primers for viral transcription. Recognizes and binds the 7-methylguanosine-containing cap of the target pre-RNA which is subsequently cleaved after 10-13 nucleotides by the viral protein PA. Plays a role in the initiation of the viral genome replication and modulates the activity of the ribonucleoprotein (RNP) complex. In addition, participates in the inhibition of type I interferon induction through interaction with and inhibition of the host mitochondrial antiviral signaling protein MAVS. [[http://www.uniprot.org/uniprot/RDRP_I68A6 RDRP_I68A6]] RNA-dependent RNA polymerase which is responsible for replication and transcription of virus RNA segments. The transcription of viral mRNAs occurs by a unique mechanism called cap-snatching. 5' methylated caps of cellular mRNAs are cleaved after 10-13 nucleotides by PA. In turn, these short capped RNAs are used as primers by PB1 for transcription of viral mRNAs. During virus replication, PB1 initiates RNA synthesis and copy vRNA into complementary RNA (cRNA) which in turn serves as a template for the production of more vRNAs. [[http://www.uniprot.org/uniprot/PA_I68A6 PA_I68A6]] Plays an essential role in viral RNA transcription and replication by forming the heterotrimeric polymerase complex together with PB1 and PB2 subunits. The complex transcribes viral mRNAs by using a unique mechanism called cap-snatching. It consists in the hijacking and cleavage of host capped pre-mRNAs. These short capped RNAs are then used as primers for viral mRNAs. The PB2 subunit is responsible for the binding of the 5' cap of cellular pre-mRNAs which are subsequently cleaved after 10-13 nucleotides by the PA subunit that carries the endonuclease activity.[HAMAP-Rule:MF_04063]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Influenza A viruses are responsible for seasonal epidemics, and pandemics can arise from the transmission of novel zoonotic influenza A viruses to humans(1,2). Influenza A viruses contain a segmented negative-sense RNA genome, which is transcribed and replicated by the viral-RNA-dependent RNA polymerase (FluPolA) composed of PB1, PB2 and PA subunits(3-5). Although the high-resolution crystal structure of FluPolA of bat influenza A virus has previously been reported(6), there are no complete structures available for human and avian FluPolA. Furthermore, the molecular mechanisms of genomic viral RNA (vRNA) replication-which proceeds through a complementary RNA (cRNA) replicative intermediate, and requires oligomerization of the polymerase(7-10)-remain largely unknown. Here, using crystallography and cryo-electron microscopy, we determine the structures of FluPolA from human influenza A/NT/60/1968 (H3N2) and avian influenza A/duck/Fujian/01/2002 (H5N1) viruses at a resolution of 3.0-4.3 A, in the presence or absence of a cRNA or vRNA template. In solution, FluPolA forms dimers of heterotrimers through the C-terminal domain of the PA subunit, the thumb subdomain of PB1 and the N1 subdomain of PB2. The cryo-electron microscopy structure of monomeric FluPolA bound to the cRNA template reveals a binding site for the 3' cRNA at the dimer interface. We use a combination of cell-based and in vitro assays to show that the interface of the FluPolA dimer is required for vRNA synthesis during replication of the viral genome. We also show that a nanobody (a single-domain antibody) that interferes with FluPolA dimerization inhibits the synthesis of vRNA and, consequently, inhibits virus replication in infected cells. Our study provides high-resolution structures of medically relevant FluPolA, as well as insights into the replication mechanisms of the viral RNA genome. In addition, our work identifies sites in FluPolA that could be targeted in the development of antiviral drugs.

-	~~Authors~~:	+	Structures of influenza A virus RNA polymerase offer insight into viral genome replication.,Fan H, Walker AP, Carrique L, Keown JR, Serna Martin I, Karia D, Sharps J, Hengrung N, Pardon E, Steyaert J, Grimes JM, Fodor E Nature. 2019 Sep;573(7773):287-290. doi: 10.1038/s41586-019-1530-7. Epub 2019 Sep, 4. PMID:31485076<ref>PMID:31485076</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6qxe" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[RNA polymerase 3D structures\|RNA polymerase 3D structures]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</SX>
		+	[[Category: I68a6]]
		+	[[Category: Large Structures]]
		+	[[Category: RNA-directed RNA polymerase]]
		+	[[Category: Carrique, L]]
		+	[[Category: Fan, H]]
		+	[[Category: Fodor, E]]
		+	[[Category: Grimes, J M]]
		+	[[Category: Keown, J R]]
		+	[[Category: Influenza some]]
		+	[[Category: Influenza dimer]]
		+	[[Category: Influenza polymerase]]
		+	[[Category: Rdrp]]
		+	[[Category: Rna binding protein]]
		+	[[Category: Rna polymerase]]

OCA at 06:06, 20 March 2019

OCA — Wed, 20 Mar 2019 06:06:58 GMT

←Older revision		Revision as of 06:06, 20 March 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6qxe is ON HOLD	+	The entry 6qxe is ON HOLD until Mar 07 2021

-	Authors: ~~Carrique, L., Keown, J.R., Fan, H., Fodor, E., Grimes, J.M.~~	+	Authors:

-	Description: ~~Influenza A virus (A/NT/60/1968) polymerase dimer of hetermotrimer in complex with 3'5' cRNA promoter and Nb8205~~	+	Description:
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Keown, J.R]]
-	[[Category: Fodor, E]]
-	[[Category: Fan, H]]
-	[[Category: Carrique, L]]
-	[[Category: Grimes, J.M]]

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

OCA — Wed, 13 Mar 2019 10:30:25 GMT

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

←Older revision

Revision as of 10:30, 13 March 2019

OCA: New page: '''Unreleased structure''' The entry 6qxe is ON HOLD Authors: Carrique, L., Keown, J.R., Fan, H., Fodor, E., Grimes, J.M. Description: Influenza A virus (A/NT/60/1968) polymerase dimer...

OCA — Wed, 13 Mar 2019 10:30:24 GMT

New page: '''Unreleased structure''' The entry 6qxe is ON HOLD Authors: Carrique, L., Keown, J.R., Fan, H., Fodor, E., Grimes, J.M. Description: Influenza A virus (A/NT/60/1968) polymerase dimer...

New page

'''Unreleased structure'''

The entry 6qxe is ON HOLD

Authors: Carrique, L., Keown, J.R., Fan, H., Fodor, E., Grimes, J.M.

Description: Influenza A virus (A/NT/60/1968) polymerase dimer of hetermotrimer in complex with 3'5' cRNA promoter and Nb8205
[[Category: Unreleased Structures]]
[[Category: Keown, J.R]]
[[Category: Fodor, E]]
[[Category: Fan, H]]
[[Category: Carrique, L]]
[[Category: Grimes, J.M]]