5zb1 - Revision history

OCA at 10:27, 27 March 2024

OCA — Wed, 27 Mar 2024 10:27:19 GMT

←Older revision		Revision as of 10:27, 27 March 2024
Line 1:		Line 1:

	==Monomeric crystal structure of orf57 from KSHV==		==Monomeric crystal structure of orf57 from KSHV==
-	<StructureSection load='5zb1' size='340' side='right' caption='[[5zb1]], [[Resolution\|resolution]] 3.06Å' scene=''>	+	<StructureSection load='5zb1' size='340' side='right'caption='[[5zb1]], [[Resolution\|resolution]] 3.06Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5zb1]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Hhv-8 Hhv-~~8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZB1 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5ZB1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5zb1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_gammaherpesvirus_8 Human gammaherpesvirus 8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZB1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZB1 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat"~~><scene name~~=~~'pdbligand=ZN:ZINC+ION'>ZN</scene~~></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]] 3.061Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~ORF57 ([http~~:/~~/www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=37296 HHV-8])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5zb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zb1 OCA], [~~http~~://pdbe.org/5zb1 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5zb1 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5zb1 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5zb1 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=5zb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zb1 OCA], [https://pdbe.org/5zb1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zb1 RCSB], [https://www.ebi.ac.uk/pdbsum/5zb1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zb1 ProSAT]</span></td></tr>
	</table>		</table>
-	~~<div style~~=~~"background-color:#fffaf0;">~~	+	== Function ==
-	=~~= Publication Abstract from PubMed~~ ==	+	[https://www.uniprot.org/uniprot/ICP27_HHV8P ICP27_HHV8P] Early protein that promotes the accumulation and nuclear export of viral intronless RNA transcripts by interacting with mRNAs and cellular export proteins. Probably acts as a viral splicing factor that regulates viral RNA splicing. Functions as a multifunctional regulator of the expression of viral lytic genes.<ref>PMID:15155762</ref>
-	~~Kaposi's sarcoma-associated herpesvirus (KSHV) is a gamma-herpesvirus closely associated with Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman disease~~. ~~Open reading frame 57 (ORF57), a viral early protein of KSHV promotes splicing, stability and translation of viral mRNA and is essential for viral lytic replication~~. ~~Previous studies demonstrated that dimerization of ORF57 stabilizes the~~ protein, which is critical for its function. However, the detailed structural basis of dimerization was not elucidated. In this study, we report the crystal structures of the C-terminal domain (CTD) of ORF57 (ORF57-CTD) in both dimer at 3.5 A and monomer at 3.0 A. Both structures reveal that ~~ORF57-CTD binds a single zinc ion through~~ the consensus zinc-binding motif at the bottom of each monomer. In addition, the N-terminal residues 167-222 of ORF57-CTD protrudes a long "arm" and holds the globular domains of the neighboring monomer, while the C-terminal residues 445-454 are locked into the globular domain in cis and the globular domains interact in trans. In vitro crosslinking and nuclear ~~translocation assays showed that either deletion~~ of the "arm" region or substitution of key residues at the globular interface led to severe dimer dissociation. Introduction of point mutation into the zinc-binding motif also led to sharp degradation of KSHV ORF57 and ~~other herpesvirus homologues~~. ~~These data indicate~~ that ~~the "arm" region, the residues at the globular interface and the zinc-binding motif are all equally important in ORF57 protein dimerization and stability~~. ~~Consistently, KSHV recombinant virus with the disrupted zinc-binding motif by point mutation exhibited~~ a ~~significant reduction in~~ the ~~RNA level~~ of ~~ORF57 downstream~~ genes ~~ORF59 and K8~~.1 and infectious virus production. Taken together, this study illustrates the first structure of KSHV ORF57-CTD and provides new insights into the understanding of ORF57 protein dimerization and stability, which would shed light on the potential design of novel therapeutics against KSHV infection and related diseases.	+
-		+
-	The crystal structure of KSHV ORF57 reveals dimeric active sites important for protein stability and function.,Yuan F, Gao ZQ, Majerciak V, Bai L, Hu ML, Lin XX, Zheng ZM, Dong YH, Lan K PLoS Pathog. 2018 Aug 10;14(8):e1007232. doi: 10.1371/journal.ppat.1007232., eCollection 2018 Aug. PMID:30096191<ref>PMID:~~30096191~~</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5zb1" style="background-color:#fffaf0;"></div~~>	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Hhv-~~8]]	+	[[Category: Human gammaherpesvirus 8]]
-	[[Category: ~~Dong, Y H~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Gao, Z Q~~]]	+	[[Category: Dong YH]]
-	[[Category: ~~Lan, K~~]]	+	[[Category: Gao ZQ]]
-	[[Category: ~~Yuan, F~~]]	+	[[Category: Lan K]]
-	[[Category: ~~Kshv orf57-ctd]]~~	+	[[Category: Yuan F]]
-	~~[[Category: Transcription~~]]	+

OCA at 15:52, 27 February 2019

OCA — Wed, 27 Feb 2019 15:52:42 GMT

←Older revision		Revision as of 15:52, 27 February 2019
Line 3:		Line 3:
	<StructureSection load='5zb1' size='340' side='right' caption='[[5zb1]], [[Resolution\|resolution]] 3.06Å' scene=''>		<StructureSection load='5zb1' size='340' side='right' caption='[[5zb1]], [[Resolution\|resolution]] 3.06Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5zb1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZB1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZB1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5zb1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Hhv-8 Hhv-8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZB1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZB1 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ORF57 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=37296 HHV-8])</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=5zb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zb1 OCA], [http://pdbe.org/5zb1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zb1 RCSB], [http://www.ebi.ac.uk/pdbsum/5zb1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zb1 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=5zb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zb1 OCA], [http://pdbe.org/5zb1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zb1 RCSB], [http://www.ebi.ac.uk/pdbsum/5zb1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zb1 ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Kaposi's sarcoma-associated herpesvirus (KSHV) is a gamma-herpesvirus closely associated with Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman disease. Open reading frame 57 (ORF57), a viral early protein of KSHV promotes splicing, stability and translation of viral mRNA and is essential for viral lytic replication. Previous studies demonstrated that dimerization of ORF57 stabilizes the protein, which is critical for its function. However, the detailed structural basis of dimerization was not elucidated. In this study, we report the crystal structures of the C-terminal domain (CTD) of ORF57 (ORF57-CTD) in both dimer at 3.5 A and monomer at 3.0 A. Both structures reveal that ORF57-CTD binds a single zinc ion through the consensus zinc-binding motif at the bottom of each monomer. In addition, the N-terminal residues 167-222 of ORF57-CTD protrudes a long "arm" and holds the globular domains of the neighboring monomer, while the C-terminal residues 445-454 are locked into the globular domain in cis and the globular domains interact in trans. In vitro crosslinking and nuclear translocation assays showed that either deletion of the "arm" region or substitution of key residues at the globular interface led to severe dimer dissociation. Introduction of point mutation into the zinc-binding motif also led to sharp degradation of KSHV ORF57 and other herpesvirus homologues. These data indicate that the "arm" region, the residues at the globular interface and the zinc-binding motif are all equally important in ORF57 protein dimerization and stability. Consistently, KSHV recombinant virus with the disrupted zinc-binding motif by point mutation exhibited a significant reduction in the RNA level of ORF57 downstream genes ORF59 and K8.1 and infectious virus production. Taken together, this study illustrates the first structure of KSHV ORF57-CTD and provides new insights into the understanding of ORF57 protein dimerization and stability, which would shed light on the potential design of novel therapeutics against KSHV infection and related diseases.
		+
		+	The crystal structure of KSHV ORF57 reveals dimeric active sites important for protein stability and function.,Yuan F, Gao ZQ, Majerciak V, Bai L, Hu ML, Lin XX, Zheng ZM, Dong YH, Lan K PLoS Pathog. 2018 Aug 10;14(8):e1007232. doi: 10.1371/journal.ppat.1007232., eCollection 2018 Aug. PMID:30096191<ref>PMID:30096191</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5zb1" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Hhv-8]]
	[[Category: Dong, Y H]]		[[Category: Dong, Y H]]
	[[Category: Gao, Z Q]]		[[Category: Gao, Z Q]]

OCA at 21:44, 9 August 2018

OCA — Thu, 09 Aug 2018 21:44:03 GMT

←Older revision		Revision as of 21:44, 9 August 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5zb1 is ~~ON HOLD~~	+	==Monomeric crystal structure of orf57 from KSHV==
-		+	<StructureSection load='5zb1' size='340' side='right' caption='[[5zb1]], [[Resolution\|resolution]] 3.06Å' scene=''>
-	~~Authors~~: ~~Gao~~, Z.Q., ~~Yuan~~, F., ~~Lan, K~~., Dong, Y.H.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5zb1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZB1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZB1 FirstGlance]. <br>
-	~~Description~~: ~~Monomeric crystal structure of orf57 from KSHV~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5zb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zb1 OCA], [http://pdbe.org/5zb1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zb1 RCSB], [http://www.ebi.ac.uk/pdbsum/5zb1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zb1 ProSAT]</span></td></tr>
		+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Dong, Y H]]
		+	[[Category: Gao, Z Q]]
		+	[[Category: Lan, K]]
	[[Category: Yuan, F]]		[[Category: Yuan, F]]
-	[[Category: ~~Lan, K~~]]	+	[[Category: Kshv orf57-ctd]]
-	[[Category: ~~Gao, Z.Q]]~~	+	[[Category: Transcription]]
-	~~[[Category: Dong, Y.H~~]]	+

OCA: Protected "5zb1" [edit=sysop:move=sysop]

OCA — Thu, 15 Feb 2018 05:13:27 GMT

Protected "5zb1" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:13, 15 February 2018

OCA: New page: '''Unreleased structure''' The entry 5zb1 is ON HOLD Authors: Gao, Z.Q., Yuan, F., Lan, K., Dong, Y.H. Description: Monomeric crystal structure of orf57 from KSHV [[Category: Unrelease...

OCA — Thu, 15 Feb 2018 05:13:26 GMT

New page: '''Unreleased structure''' The entry 5zb1 is ON HOLD Authors: Gao, Z.Q., Yuan, F., Lan, K., Dong, Y.H. Description: Monomeric crystal structure of orf57 from KSHV [[Category: Unrelease...

New page

'''Unreleased structure'''

The entry 5zb1 is ON HOLD

Authors: Gao, Z.Q., Yuan, F., Lan, K., Dong, Y.H.

Description: Monomeric crystal structure of orf57 from KSHV
[[Category: Unreleased Structures]]
[[Category: Yuan, F]]
[[Category: Lan, K]]
[[Category: Gao, Z.Q]]
[[Category: Dong, Y.H]]