6mx7 - Revision history

OCA at 14:45, 13 March 2024

2024-03-13T14:45:40Z

←Older revision		Revision as of 14:45, 13 March 2024
Line 3:		Line 3:
	<SX load='6mx7' size='340' side='right' viewer='molstar' caption='[[6mx7]], [[Resolution\|resolution]] 4.80Å' scene=''>		<SX load='6mx7' size='340' side='right' viewer='molstar' caption='[[6mx7]], [[Resolution\|resolution]] 4.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6mx7]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Eeev Eeev~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MX7 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6MX7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6mx7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Eastern_equine_encephalitis_virus Eastern equine encephalitis virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MX7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MX7 FirstGlance]. <br>
-	</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=6mx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mx7 OCA], [~~http~~://pdbe.org/6mx7 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6mx7 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6mx7 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6mx7 ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 4.8Å</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=6mx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mx7 OCA], [https://pdbe.org/6mx7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mx7 RCSB], [https://www.ebi.ac.uk/pdbsum/6mx7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mx7 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/POLS_EEEV3 POLS_EEEV3]] Capsid protein: Possesses a protease activity that results in its autocatalytic cleavage from the nascent structural protein. Following its self-cleavage, the capsid protein transiently associates with ribosomes, and within several minutes the protein binds to viral RNA and rapidly assembles into icosahedric core particles. The resulting nucleocapsid eventually associates with the cytoplasmic domain of the spike glycoprotein E2 at the cell membrane, leading to budding and formation of mature virions. In case of infection, new virions attach to target cells and after clathrin-mediated endocytosis their membrane fuses with the host endosomal membrane. This leads to the release of the nucleocapsid into the cytoplasm, followed by an uncoating event necessary for the genomic RNA to become accessible. The uncoating might be triggered by the interaction of capsid proteins with ribosomes. Binding of ribosomes would release the genomic RNA since the same region is genomic RNA-binding and ribosome-binding.[UniProtKB:P03315] Assembly protein E3: Provides the signal sequence for the translocation of the precursor of protein E3/E2 to the host endoplasmic reticulum. Mediates pH protection of spike glycoprotein E1 during the transport via the secretory pathway.[UniProtKB:P03315] Spike glycoprotein E2: Plays a role in viral attachment to target host cell, by binding to the cell receptor. Synthesized as a p62 precursor which is processed by furin at the cell membrane just before virion budding, giving rise to E2-E1 heterodimer. The p62-E1 heterodimer is stable, whereas E2-E1 is unstable and dissociate at low pH. p62 is processed at the last step, presumably to avoid E1 fusion activation before its final export to cell surface. E2 C-terminus contains a transitory transmembrane that would be disrupted by palmitoylation, resulting in reorientation of the C-terminal tail from lumenal to cytoplasmic side. This step is critical since E2 C-terminus is involved in budding by interacting with capsid proteins. This release of E2 C-terminus in cytoplasm occurs lately in protein export, and precludes premature assembly of particles at the endoplasmic reticulum membrane.[UniProtKB:P03315] 6K protein: Constitutive membrane protein involved in virus glycoprotein processing, cell permeabilization, and the budding of viral particles. Disrupts the calcium homeostasis of the cell, probably at the endoplasmic reticulum level. This leads to cytoplasmic calcium elevation. Because of its lipophilic properties, the 6K protein is postulated to influence the selection of lipids that interact with the transmembrane domains of the glycoproteins, which, in turn, affects the deformability of the bilayer required for the extreme curvature that occurs as budding proceeds. Present in low amount in virions, about 3% compared to viral glycoproteins.[UniProtKB:P03315] Spike glycoprotein E1: Class II viral fusion protein. Fusion activity is inactive as long as E1 is bound to E2 in mature virion. After virus attachment to target cell and endocytosis, acidification of the endosome would induce dissociation of E1/E2 heterodimer and concomitant trimerization of the E1 subunits. This E1 trimer is fusion active, and promotes release of viral nucleocapsid in cytoplasm after endosome and viral membrane fusion. Efficient fusion requires the presence of cholesterol and sphingolipid in the target membrane. Fusion is optimal at levels of about 1 molecule of cholesterol per 2 molecules of phospholipids, and is specific for sterols containing a 3-beta-hydroxyl group.[UniProtKB:P03315]	+	[https://www.uniprot.org/uniprot/POLS_EEEV3 POLS_EEEV3] Capsid protein: Possesses a protease activity that results in its autocatalytic cleavage from the nascent structural protein. Following its self-cleavage, the capsid protein transiently associates with ribosomes, and within several minutes the protein binds to viral RNA and rapidly assembles into icosahedric core particles. The resulting nucleocapsid eventually associates with the cytoplasmic domain of the spike glycoprotein E2 at the cell membrane, leading to budding and formation of mature virions. In case of infection, new virions attach to target cells and after clathrin-mediated endocytosis their membrane fuses with the host endosomal membrane. This leads to the release of the nucleocapsid into the cytoplasm, followed by an uncoating event necessary for the genomic RNA to become accessible. The uncoating might be triggered by the interaction of capsid proteins with ribosomes. Binding of ribosomes would release the genomic RNA since the same region is genomic RNA-binding and ribosome-binding.[UniProtKB:P03315] Assembly protein E3: Provides the signal sequence for the translocation of the precursor of protein E3/E2 to the host endoplasmic reticulum. Mediates pH protection of spike glycoprotein E1 during the transport via the secretory pathway.[UniProtKB:P03315] Spike glycoprotein E2: Plays a role in viral attachment to target host cell, by binding to the cell receptor. Synthesized as a p62 precursor which is processed by furin at the cell membrane just before virion budding, giving rise to E2-E1 heterodimer. The p62-E1 heterodimer is stable, whereas E2-E1 is unstable and dissociate at low pH. p62 is processed at the last step, presumably to avoid E1 fusion activation before its final export to cell surface. E2 C-terminus contains a transitory transmembrane that would be disrupted by palmitoylation, resulting in reorientation of the C-terminal tail from lumenal to cytoplasmic side. This step is critical since E2 C-terminus is involved in budding by interacting with capsid proteins. This release of E2 C-terminus in cytoplasm occurs lately in protein export, and precludes premature assembly of particles at the endoplasmic reticulum membrane.[UniProtKB:P03315] 6K protein: Constitutive membrane protein involved in virus glycoprotein processing, cell permeabilization, and the budding of viral particles. Disrupts the calcium homeostasis of the cell, probably at the endoplasmic reticulum level. This leads to cytoplasmic calcium elevation. Because of its lipophilic properties, the 6K protein is postulated to influence the selection of lipids that interact with the transmembrane domains of the glycoproteins, which, in turn, affects the deformability of the bilayer required for the extreme curvature that occurs as budding proceeds. Present in low amount in virions, about 3% compared to viral glycoproteins.[UniProtKB:P03315] Spike glycoprotein E1: Class II viral fusion protein. Fusion activity is inactive as long as E1 is bound to E2 in mature virion. After virus attachment to target cell and endocytosis, acidification of the endosome would induce dissociation of E1/E2 heterodimer and concomitant trimerization of the E1 subunits. This E1 trimer is fusion active, and promotes release of viral nucleocapsid in cytoplasm after endosome and viral membrane fusion. Efficient fusion requires the presence of cholesterol and sphingolipid in the target membrane. Fusion is optimal at levels of about 1 molecule of cholesterol per 2 molecules of phospholipids, and is specific for sterols containing a 3-beta-hydroxyl group.[UniProtKB:P03315]
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Alphaviruses are enveloped pathogens that cause arthritis and encephalitis. Here, we report a 4.4-A cryoelectron microscopy (cryo-EM) structure of eastern equine encephalitis virus (EEEV), an alphavirus that causes fatal encephalitis in humans. Our analysis provides insights into viral entry into host cells. The envelope protein E2 showed a binding site for the cellular attachment factor heparan sulfate. The presence of a cryptic E2 glycan suggests how EEEV escapes surveillance by lectin-expressing myeloid lineage cells, which are sentinels of the immune system. A mechanism for nucleocapsid core release and disassembly upon viral entry was inferred based on pH changes and capsid dissociation from envelope proteins. The EEEV capsid structure showed a viral RNA genome binding site adjacent to a ribosome binding site for viral genome translation following genome release. Using five Fab-EEEV complexes derived from neutralizing antibodies, our investigation provides insights into EEEV host cell interactions and protective epitopes relevant to vaccine design.	+

-	Cryo-EM Structures of Eastern Equine Encephalitis Virus Reveal Mechanisms of Virus Disassembly and Antibody Neutralization.,Hasan SS, Sun C, Kim AS, Watanabe Y, Chen CL, Klose T, Buda G, Crispin M, Diamond MS, Klimstra WB, Rossmann MG Cell Rep. 2018 Dec 11;25(11):3136-3147.e5. doi: 10.1016/j.celrep.2018.11.067. PMID:30540945<ref>PMID:30540945</ref>	+	==See Also==
-		+	*[[Virus coat proteins 3D structures\|Virus coat proteins 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class~~=~~"pdbe-citations 6mx7" style~~=~~"background-color:#fffaf0;"></div>~~	+
-	~~== References~~ ==	+
-	~~<references/>~~	+
	__TOC__		__TOC__
	</SX>		</SX>
-	[[Category: ~~Eeev~~]]	+	[[Category: Eastern equine encephalitis virus]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Buda, G]]	+	[[Category: Buda G]]
-	[[Category: Chen~~, C L~~]]	+	[[Category: Chen CL]]
-	[[Category: Crispin, M]]	+	[[Category: Crispin M]]
-	[[Category: Diamond~~, M S~~]]	+	[[Category: Diamond MS]]
-	[[Category: Hasan~~, S S~~]]	+	[[Category: Hasan SS]]
-	[[Category: Kim~~, A S~~]]	+	[[Category: Kim AS]]
-	[[Category: Klimstra~~, W B~~]]	+	[[Category: Klimstra WB]]
-	[[Category: Klose, T]]	+	[[Category: Klose T]]
-	[[Category: Rossmann~~, M G~~]]	+	[[Category: Rossmann MG]]
-	[[Category: Sun, C]]	+	[[Category: Sun C]]
-	[[Category: Watanabe, Y]]	+	[[Category: Watanabe Y]]
-	~~[[Category: Alphavirus]]~~	+
-	~~[[Category: Eastern equine encephalitis virus]]~~	+
-	~~[[Category: Sindbi]]~~	+
-	~~[[Category: Virus~~]]	+

OCA at 02:59, 11 April 2020

2020-04-11T02:59:55Z

←Older revision		Revision as of 02:59, 11 April 2020
Line 3:		Line 3:
	<SX load='6mx7' size='340' side='right' viewer='molstar' caption='[[6mx7]], [[Resolution\|resolution]] 4.80Å' scene=''>		<SX load='6mx7' size='340' side='right' viewer='molstar' caption='[[6mx7]], [[Resolution\|resolution]] 4.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6mx7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Eeev Eeev]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MX7 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6MX7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6mx7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Eeev Eeev]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MX7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6MX7 FirstGlance]. <br>
-	</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=6mx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mx7 OCA], [http://pdbe.org/6mx7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mx7 RCSB], [http://www.ebi.ac.uk/pdbsum/6mx7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mx7 ProSAT]</span></td></tr>	+	</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=6mx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mx7 OCA], [http://pdbe.org/6mx7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mx7 RCSB], [http://www.ebi.ac.uk/pdbsum/6mx7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mx7 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 22:39, 6 March 2020

2020-03-06T22:39:36Z

←Older revision		Revision as of 22:39, 6 March 2020
Line 1:		Line 1:

	==CryoEM structure of chimeric Eastern Equine Encephalitis Virus: Genome-Binding Capsid N-terminal Domain==		==CryoEM structure of chimeric Eastern Equine Encephalitis Virus: Genome-Binding Capsid N-terminal Domain==
-	<~~StructureSection~~ load='6mx7' size='340' side='right'caption='[[6mx7]], [[Resolution\|resolution]] 4.80Å' scene=''>	+	<SX load='6mx7' size='340' side='right' viewer='molstar' caption='[[6mx7]], [[Resolution\|resolution]] 4.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6mx7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Eeev Eeev]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MX7 FirstGlance]. <br>		<table><tr><td colspan='2'>[[6mx7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Eeev Eeev]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MX7 FirstGlance]. <br>
Line 20:		Line 20:
	<references/>		<references/>
	__TOC__		__TOC__
-	</~~StructureSection~~>	+	</SX>
	[[Category: Eeev]]		[[Category: Eeev]]
	[[Category: Large Structures]]		[[Category: Large Structures]]

OCA at 11:13, 18 December 2019

2019-12-18T11:13:57Z

←Older revision		Revision as of 11:13, 18 December 2019
Line 1:		Line 1:

	==CryoEM structure of chimeric Eastern Equine Encephalitis Virus: Genome-Binding Capsid N-terminal Domain==		==CryoEM structure of chimeric Eastern Equine Encephalitis Virus: Genome-Binding Capsid N-terminal Domain==
-	<StructureSection load='6mx7' size='340' side='right' caption='[[6mx7]], [[Resolution\|resolution]] 4.80Å' scene=''>	+	<StructureSection load='6mx7' size='340' side='right'caption='[[6mx7]], [[Resolution\|resolution]] 4.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6mx7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Eeev Eeev]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MX7 FirstGlance]. <br>		<table><tr><td colspan='2'>[[6mx7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Eeev Eeev]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MX7 FirstGlance]. <br>
Line 22:		Line 22:
	</StructureSection>		</StructureSection>
	[[Category: Eeev]]		[[Category: Eeev]]
		+	[[Category: Large Structures]]
	[[Category: Buda, G]]		[[Category: Buda, G]]
	[[Category: Chen, C L]]		[[Category: Chen, C L]]

OCA at 08:47, 26 December 2018

2018-12-26T08:47:31Z

←Older revision		Revision as of 08:47, 26 December 2018
Line 3:		Line 3:
	<StructureSection load='6mx7' size='340' side='right' caption='[[6mx7]], [[Resolution\|resolution]] 4.80Å' scene=''>		<StructureSection load='6mx7' size='340' side='right' caption='[[6mx7]], [[Resolution\|resolution]] 4.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6mx7]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MX7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6mx7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Eeev Eeev]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MX7 FirstGlance]. <br>
	</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=6mx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mx7 OCA], [http://pdbe.org/6mx7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mx7 RCSB], [http://www.ebi.ac.uk/pdbsum/6mx7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mx7 ProSAT]</span></td></tr>		</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=6mx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mx7 OCA], [http://pdbe.org/6mx7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mx7 RCSB], [http://www.ebi.ac.uk/pdbsum/6mx7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mx7 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/POLS_EEEV3 POLS_EEEV3]] Capsid protein: Possesses a protease activity that results in its autocatalytic cleavage from the nascent structural protein. Following its self-cleavage, the capsid protein transiently associates with ribosomes, and within several minutes the protein binds to viral RNA and rapidly assembles into icosahedric core particles. The resulting nucleocapsid eventually associates with the cytoplasmic domain of the spike glycoprotein E2 at the cell membrane, leading to budding and formation of mature virions. In case of infection, new virions attach to target cells and after clathrin-mediated endocytosis their membrane fuses with the host endosomal membrane. This leads to the release of the nucleocapsid into the cytoplasm, followed by an uncoating event necessary for the genomic RNA to become accessible. The uncoating might be triggered by the interaction of capsid proteins with ribosomes. Binding of ribosomes would release the genomic RNA since the same region is genomic RNA-binding and ribosome-binding.[UniProtKB:P03315] Assembly protein E3: Provides the signal sequence for the translocation of the precursor of protein E3/E2 to the host endoplasmic reticulum. Mediates pH protection of spike glycoprotein E1 during the transport via the secretory pathway.[UniProtKB:P03315] Spike glycoprotein E2: Plays a role in viral attachment to target host cell, by binding to the cell receptor. Synthesized as a p62 precursor which is processed by furin at the cell membrane just before virion budding, giving rise to E2-E1 heterodimer. The p62-E1 heterodimer is stable, whereas E2-E1 is unstable and dissociate at low pH. p62 is processed at the last step, presumably to avoid E1 fusion activation before its final export to cell surface. E2 C-terminus contains a transitory transmembrane that would be disrupted by palmitoylation, resulting in reorientation of the C-terminal tail from lumenal to cytoplasmic side. This step is critical since E2 C-terminus is involved in budding by interacting with capsid proteins. This release of E2 C-terminus in cytoplasm occurs lately in protein export, and precludes premature assembly of particles at the endoplasmic reticulum membrane.[UniProtKB:P03315] 6K protein: Constitutive membrane protein involved in virus glycoprotein processing, cell permeabilization, and the budding of viral particles. Disrupts the calcium homeostasis of the cell, probably at the endoplasmic reticulum level. This leads to cytoplasmic calcium elevation. Because of its lipophilic properties, the 6K protein is postulated to influence the selection of lipids that interact with the transmembrane domains of the glycoproteins, which, in turn, affects the deformability of the bilayer required for the extreme curvature that occurs as budding proceeds. Present in low amount in virions, about 3% compared to viral glycoproteins.[UniProtKB:P03315] Spike glycoprotein E1: Class II viral fusion protein. Fusion activity is inactive as long as E1 is bound to E2 in mature virion. After virus attachment to target cell and endocytosis, acidification of the endosome would induce dissociation of E1/E2 heterodimer and concomitant trimerization of the E1 subunits. This E1 trimer is fusion active, and promotes release of viral nucleocapsid in cytoplasm after endosome and viral membrane fusion. Efficient fusion requires the presence of cholesterol and sphingolipid in the target membrane. Fusion is optimal at levels of about 1 molecule of cholesterol per 2 molecules of phospholipids, and is specific for sterols containing a 3-beta-hydroxyl group.[UniProtKB:P03315]		[[http://www.uniprot.org/uniprot/POLS_EEEV3 POLS_EEEV3]] Capsid protein: Possesses a protease activity that results in its autocatalytic cleavage from the nascent structural protein. Following its self-cleavage, the capsid protein transiently associates with ribosomes, and within several minutes the protein binds to viral RNA and rapidly assembles into icosahedric core particles. The resulting nucleocapsid eventually associates with the cytoplasmic domain of the spike glycoprotein E2 at the cell membrane, leading to budding and formation of mature virions. In case of infection, new virions attach to target cells and after clathrin-mediated endocytosis their membrane fuses with the host endosomal membrane. This leads to the release of the nucleocapsid into the cytoplasm, followed by an uncoating event necessary for the genomic RNA to become accessible. The uncoating might be triggered by the interaction of capsid proteins with ribosomes. Binding of ribosomes would release the genomic RNA since the same region is genomic RNA-binding and ribosome-binding.[UniProtKB:P03315] Assembly protein E3: Provides the signal sequence for the translocation of the precursor of protein E3/E2 to the host endoplasmic reticulum. Mediates pH protection of spike glycoprotein E1 during the transport via the secretory pathway.[UniProtKB:P03315] Spike glycoprotein E2: Plays a role in viral attachment to target host cell, by binding to the cell receptor. Synthesized as a p62 precursor which is processed by furin at the cell membrane just before virion budding, giving rise to E2-E1 heterodimer. The p62-E1 heterodimer is stable, whereas E2-E1 is unstable and dissociate at low pH. p62 is processed at the last step, presumably to avoid E1 fusion activation before its final export to cell surface. E2 C-terminus contains a transitory transmembrane that would be disrupted by palmitoylation, resulting in reorientation of the C-terminal tail from lumenal to cytoplasmic side. This step is critical since E2 C-terminus is involved in budding by interacting with capsid proteins. This release of E2 C-terminus in cytoplasm occurs lately in protein export, and precludes premature assembly of particles at the endoplasmic reticulum membrane.[UniProtKB:P03315] 6K protein: Constitutive membrane protein involved in virus glycoprotein processing, cell permeabilization, and the budding of viral particles. Disrupts the calcium homeostasis of the cell, probably at the endoplasmic reticulum level. This leads to cytoplasmic calcium elevation. Because of its lipophilic properties, the 6K protein is postulated to influence the selection of lipids that interact with the transmembrane domains of the glycoproteins, which, in turn, affects the deformability of the bilayer required for the extreme curvature that occurs as budding proceeds. Present in low amount in virions, about 3% compared to viral glycoproteins.[UniProtKB:P03315] Spike glycoprotein E1: Class II viral fusion protein. Fusion activity is inactive as long as E1 is bound to E2 in mature virion. After virus attachment to target cell and endocytosis, acidification of the endosome would induce dissociation of E1/E2 heterodimer and concomitant trimerization of the E1 subunits. This E1 trimer is fusion active, and promotes release of viral nucleocapsid in cytoplasm after endosome and viral membrane fusion. Efficient fusion requires the presence of cholesterol and sphingolipid in the target membrane. Fusion is optimal at levels of about 1 molecule of cholesterol per 2 molecules of phospholipids, and is specific for sterols containing a 3-beta-hydroxyl group.[UniProtKB:P03315]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Alphaviruses are enveloped pathogens that cause arthritis and encephalitis. Here, we report a 4.4-A cryoelectron microscopy (cryo-EM) structure of eastern equine encephalitis virus (EEEV), an alphavirus that causes fatal encephalitis in humans. Our analysis provides insights into viral entry into host cells. The envelope protein E2 showed a binding site for the cellular attachment factor heparan sulfate. The presence of a cryptic E2 glycan suggests how EEEV escapes surveillance by lectin-expressing myeloid lineage cells, which are sentinels of the immune system. A mechanism for nucleocapsid core release and disassembly upon viral entry was inferred based on pH changes and capsid dissociation from envelope proteins. The EEEV capsid structure showed a viral RNA genome binding site adjacent to a ribosome binding site for viral genome translation following genome release. Using five Fab-EEEV complexes derived from neutralizing antibodies, our investigation provides insights into EEEV host cell interactions and protective epitopes relevant to vaccine design.
		+
		+	Cryo-EM Structures of Eastern Equine Encephalitis Virus Reveal Mechanisms of Virus Disassembly and Antibody Neutralization.,Hasan SS, Sun C, Kim AS, Watanabe Y, Chen CL, Klose T, Buda G, Crispin M, Diamond MS, Klimstra WB, Rossmann MG Cell Rep. 2018 Dec 11;25(11):3136-3147.e5. doi: 10.1016/j.celrep.2018.11.067. PMID:30540945<ref>PMID:30540945</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6mx7" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Eeev]]
	[[Category: Buda, G]]		[[Category: Buda, G]]
	[[Category: Chen, C L]]		[[Category: Chen, C L]]
Line 23:		Line 35:
	[[Category: Alphavirus]]		[[Category: Alphavirus]]
	[[Category: Eastern equine encephalitis virus]]		[[Category: Eastern equine encephalitis virus]]
-	[[Category: Eeev]]
	[[Category: Sindbi]]		[[Category: Sindbi]]
	[[Category: Virus]]		[[Category: Virus]]

OCA at 08:35, 19 December 2018

2018-12-19T08:35:18Z

←Older revision		Revision as of 08:35, 19 December 2018
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-	'''Unreleased structure'''

-	~~The entry~~ 6mx7 ~~is ON HOLD until Paper Publication~~	+	==CryoEM structure of chimeric Eastern Equine Encephalitis Virus: Genome-Binding Capsid N-terminal Domain==
-		+	<StructureSection load='6mx7' size='340' side='right' caption='[[6mx7]], [[Resolution\|resolution]] 4.80Å' scene=''>
-	~~Authors~~: ~~Hasan~~, S.S., ~~Sun~~, C., ~~Kim~~, A.S., ~~Watanabe~~, Y., ~~Chen~~, C.L., ~~Klose~~, T., ~~Buda~~, G., ~~Crispin~~, M., ~~Diamond~~, M.S., ~~Klimstra~~, W.B., ~~Rossmann~~, M.G.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6mx7]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MX7 FirstGlance]. <br>
-	~~Description: CryoEM structure~~ of ~~chimeric Eastern Equine Encephalitis Virus: Genome~~-~~Binding Capsid N~~-~~terminal Domain~~	+	</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=6mx7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mx7 OCA], [http://pdbe.org/6mx7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mx7 RCSB], [http://www.ebi.ac.uk/pdbsum/6mx7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mx7 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
-	[[Category: ~~Diamond~~, ~~M.S~~]]	+	== Function ==
		+	[[http://www.uniprot.org/uniprot/POLS_EEEV3 POLS_EEEV3]] Capsid protein: Possesses a protease activity that results in its autocatalytic cleavage from the nascent structural protein. Following its self-cleavage, the capsid protein transiently associates with ribosomes, and within several minutes the protein binds to viral RNA and rapidly assembles into icosahedric core particles. The resulting nucleocapsid eventually associates with the cytoplasmic domain of the spike glycoprotein E2 at the cell membrane, leading to budding and formation of mature virions. In case of infection, new virions attach to target cells and after clathrin-mediated endocytosis their membrane fuses with the host endosomal membrane. This leads to the release of the nucleocapsid into the cytoplasm, followed by an uncoating event necessary for the genomic RNA to become accessible. The uncoating might be triggered by the interaction of capsid proteins with ribosomes. Binding of ribosomes would release the genomic RNA since the same region is genomic RNA-binding and ribosome-binding.[UniProtKB:P03315] Assembly protein E3: Provides the signal sequence for the translocation of the precursor of protein E3/E2 to the host endoplasmic reticulum. Mediates pH protection of spike glycoprotein E1 during the transport via the secretory pathway.[UniProtKB:P03315] Spike glycoprotein E2: Plays a role in viral attachment to target host cell, by binding to the cell receptor. Synthesized as a p62 precursor which is processed by furin at the cell membrane just before virion budding, giving rise to E2-E1 heterodimer. The p62-E1 heterodimer is stable, whereas E2-E1 is unstable and dissociate at low pH. p62 is processed at the last step, presumably to avoid E1 fusion activation before its final export to cell surface. E2 C-terminus contains a transitory transmembrane that would be disrupted by palmitoylation, resulting in reorientation of the C-terminal tail from lumenal to cytoplasmic side. This step is critical since E2 C-terminus is involved in budding by interacting with capsid proteins. This release of E2 C-terminus in cytoplasm occurs lately in protein export, and precludes premature assembly of particles at the endoplasmic reticulum membrane.[UniProtKB:P03315] 6K protein: Constitutive membrane protein involved in virus glycoprotein processing, cell permeabilization, and the budding of viral particles. Disrupts the calcium homeostasis of the cell, probably at the endoplasmic reticulum level. This leads to cytoplasmic calcium elevation. Because of its lipophilic properties, the 6K protein is postulated to influence the selection of lipids that interact with the transmembrane domains of the glycoproteins, which, in turn, affects the deformability of the bilayer required for the extreme curvature that occurs as budding proceeds. Present in low amount in virions, about 3% compared to viral glycoproteins.[UniProtKB:P03315] Spike glycoprotein E1: Class II viral fusion protein. Fusion activity is inactive as long as E1 is bound to E2 in mature virion. After virus attachment to target cell and endocytosis, acidification of the endosome would induce dissociation of E1/E2 heterodimer and concomitant trimerization of the E1 subunits. This E1 trimer is fusion active, and promotes release of viral nucleocapsid in cytoplasm after endosome and viral membrane fusion. Efficient fusion requires the presence of cholesterol and sphingolipid in the target membrane. Fusion is optimal at levels of about 1 molecule of cholesterol per 2 molecules of phospholipids, and is specific for sterols containing a 3-beta-hydroxyl group.[UniProtKB:P03315]
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Buda, G]]
		+	[[Category: Chen, C L]]
	[[Category: Crispin, M]]		[[Category: Crispin, M]]
		+	[[Category: Diamond, M S]]
		+	[[Category: Hasan, S S]]
		+	[[Category: Kim, A S]]
		+	[[Category: Klimstra, W B]]
		+	[[Category: Klose, T]]
		+	[[Category: Rossmann, M G]]
	[[Category: Sun, C]]		[[Category: Sun, C]]
-	[[Category: Klimstra, W.B]]
-	[[Category: Rossmann, M.G]]
-	[[Category: Hasan, S.S]]
-	[[Category: Klose, T]]
-	[[Category: Buda, G]]
-	[[Category: Kim, A.S]]
-	[[Category: Chen, C.L]]
	[[Category: Watanabe, Y]]		[[Category: Watanabe, Y]]
		+	[[Category: Alphavirus]]
		+	[[Category: Eastern equine encephalitis virus]]
		+	[[Category: Eeev]]
		+	[[Category: Sindbi]]
		+	[[Category: Virus]]

OCA at 05:13, 5 December 2018

2018-12-05T05:13:42Z

←Older revision		Revision as of 05:13, 5 December 2018
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6mx7 is ON HOLD	+	The entry 6mx7 is ON HOLD until Paper Publication

	Authors: Hasan, S.S., Sun, C., Kim, A.S., Watanabe, Y., Chen, C.L., Klose, T., Buda, G., Crispin, M., Diamond, M.S., Klimstra, W.B., Rossmann, M.G.		Authors: Hasan, S.S., Sun, C., Kim, A.S., Watanabe, Y., Chen, C.L., Klose, T., Buda, G., Crispin, M., Diamond, M.S., Klimstra, W.B., Rossmann, M.G.
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	Description: CryoEM structure of chimeric Eastern Equine Encephalitis Virus: Genome-Binding Capsid N-terminal Domain		Description: CryoEM structure of chimeric Eastern Equine Encephalitis Virus: Genome-Binding Capsid N-terminal Domain
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: Chen, C.L]]
-	[[Category: Watanabe, Y]]
	[[Category: Diamond, M.S]]		[[Category: Diamond, M.S]]
	[[Category: Crispin, M]]		[[Category: Crispin, M]]
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	[[Category: Buda, G]]		[[Category: Buda, G]]
	[[Category: Kim, A.S]]		[[Category: Kim, A.S]]
		+	[[Category: Chen, C.L]]
		+	[[Category: Watanabe, Y]]

OCA at 19:03, 2 December 2018

2018-12-02T19:03:03Z

←Older revision		Revision as of 19:03, 2 December 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6mx7 is ON HOLD ~~until sometime in the future~~	+	The entry 6mx7 is ON HOLD

	Authors: Hasan, S.S., Sun, C., Kim, A.S., Watanabe, Y., Chen, C.L., Klose, T., Buda, G., Crispin, M., Diamond, M.S., Klimstra, W.B., Rossmann, M.G.		Authors: Hasan, S.S., Sun, C., Kim, A.S., Watanabe, Y., Chen, C.L., Klose, T., Buda, G., Crispin, M., Diamond, M.S., Klimstra, W.B., Rossmann, M.G.

OCA at 06:39, 14 November 2018

2018-11-14T06:39:25Z

←Older revision		Revision as of 06:39, 14 November 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6mx7 is ON HOLD	+	The entry 6mx7 is ON HOLD until sometime in the future

	Authors: Hasan, S.S., Sun, C., Kim, A.S., Watanabe, Y., Chen, C.L., Klose, T., Buda, G., Crispin, M., Diamond, M.S., Klimstra, W.B., Rossmann, M.G.		Authors: Hasan, S.S., Sun, C., Kim, A.S., Watanabe, Y., Chen, C.L., Klose, T., Buda, G., Crispin, M., Diamond, M.S., Klimstra, W.B., Rossmann, M.G.
Line 7:		Line 7:
	Description: CryoEM structure of chimeric Eastern Equine Encephalitis Virus: Genome-Binding Capsid N-terminal Domain		Description: CryoEM structure of chimeric Eastern Equine Encephalitis Virus: Genome-Binding Capsid N-terminal Domain
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
		+	[[Category: Chen, C.L]]
		+	[[Category: Watanabe, Y]]
	[[Category: Diamond, M.S]]		[[Category: Diamond, M.S]]
	[[Category: Crispin, M]]		[[Category: Crispin, M]]
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	[[Category: Buda, G]]		[[Category: Buda, G]]
	[[Category: Kim, A.S]]		[[Category: Kim, A.S]]
-	[[Category: Chen, C.L]]
-	[[Category: Watanabe, Y]]

OCA: Protected "6mx7" [edit=sysop:move=sysop]

2018-11-07T10:55:38Z

Protected "6mx7" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:55, 7 November 2018