6eay - Revision history

OCA at 06:22, 11 October 2023

OCA — Wed, 11 Oct 2023 06:22:08 GMT

←Older revision		Revision as of 06:22, 11 October 2023
Line 3:		Line 3:
	<StructureSection load='6eay' size='340' side='right'caption='[[6eay]], [[Resolution\|resolution]] 3.72Å' scene=''>		<StructureSection load='6eay' size='340' side='right'caption='[[6eay]], [[Resolution\|resolution]] 3.72Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6eay]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Crab~~-~~eating_macaque Crab~~-~~eating macaque~~] and [~~http~~://en.wikipedia.org/wiki/~~Ebov-may Ebov-may~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EAY OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6EAY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6eay]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Ebola_virus_-_Mayinga,_Zaire,_1976 Ebola virus - Mayinga, Zaire, 1976] and [https://en.wikipedia.org/wiki/Macaca_fascicularis Macaca fascicularis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EAY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EAY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=~~NAG~~:~~N-ACETYL~~-D-~~GLUCOSAMINE~~'>~~NAG~~</scene>, <scene name='pdbligand=~~MAN~~:~~ALPHA~~-D-~~MANNOSE~~'>~~MAN~~</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]] 3.72Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=128952 EBOV-May])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=6eay FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eay OCA], [~~http~~://pdbe.org/6eay PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6eay RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6eay PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6eay 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=6eay FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eay OCA], [https://pdbe.org/6eay PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6eay RCSB], [https://www.ebi.ac.uk/pdbsum/6eay PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6eay ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/VGP_EBOZM VGP_EBOZM]] GP1 is responsible for binding to the receptor(s) on target cells. Interacts with CD209/DC-SIGN and CLEC4M/DC-SIGNR which act as cofactors for virus entry into the host cell. Binding to CD209 and CLEC4M, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses, facilitate infection of macrophages and endothelial cells. These interactions not only facilitate virus cell entry, but also allow capture of viral particles by DCs and subsequent transmission to susceptible cells without DCs infection (trans infection). Binding to the macrophage specific lectin CLEC10A also seem to enhance virus infectivity. Interaction with FOLR1/folate receptor alpha may be a cofactor for virus entry in some cell types, although results are contradictory. Members of the Tyro3 receptor tyrosine kinase family also seem to be cell entry factors in filovirus infection. Once attached, the virions are internalized through clathrin-dependent endocytosis and/or macropinocytosis. After internalization of the virus into the endosomes of the host cell, proteolysis of GP1 by two cysteine proteases, CTSB/cathepsin B and CTSL/cathepsin L presumably induces a conformational change of GP2, unmasking its fusion peptide and initiating membranes fusion.<ref>PMID:10932225</ref> <ref>PMID:12050398</ref> <ref>PMID:16051836</ref> <ref>PMID:15681442</ref> <ref>PMID:16603527</ref> <ref>PMID:16775318</ref> <ref>PMID:20862315</ref> <ref>PMID:20202662</ref> GP2 acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in GP2, releasing the fusion hydrophobic peptide.<ref>PMID:10932225</ref> <ref>PMID:12050398</ref> <ref>PMID:16051836</ref> <ref>PMID:15681442</ref> <ref>PMID:16603527</ref> <ref>PMID:16775318</ref> <ref>PMID:20862315</ref> <ref>PMID:20202662</ref> GP1,2 mediates endothelial cell activation and decreases endothelial barrier function. Mediates activation of primary macrophages. At terminal stages of the viral infection, when its expression is high, GP1,2 down-modulates the expression of various host cell surface molecules that are essential for immune surveillance and cell adhesion. Down-modulates integrins ITGA1, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGAV and ITGB1. GP1,2 alters the cellular recycling of the dimer alpha-V/beta-3 via a dynamin-dependent pathway. Decrease in the host cell surface expression of various adhesion molecules may lead to cell detachment, contributing to the disruption of blood vessel integrity and hemorrhages developed during Ebola virus infection (cytotoxicity). This cytotoxicity appears late in the infection, only after the massive release of viral particles by infected cells. Down-modulation of host MHC-I, leading to altered recognition by immune cells, may explain the immune suppression and inflammatory dysfunction linked to Ebola infection. Also down-modulates EGFR surface expression.<ref>PMID:10932225</ref> <ref>PMID:12050398</ref> <ref>PMID:16051836</ref> <ref>PMID:15681442</ref> <ref>PMID:16603527</ref> <ref>PMID:16775318</ref> <ref>PMID:20862315</ref> <ref>PMID:20202662</ref> GP2delta is part of the complex GP1,2delta released by host ADAM17 metalloprotease. This secreted complex may play a role in the pathogenesis of the virus by efficiently blocking the neutralizing antibodies that would otherwise neutralize the virus surface glycoproteins GP1,2. Might therefore contribute to the lack of inflammatory reaction seen during infection in spite the of extensive necrosis and massive virus production. GP1,2delta does not seem to be involved in activation of primary macrophages.<ref>PMID:10932225</ref> <ref>PMID:12050398</ref> <ref>PMID:16051836</ref> <ref>PMID:15681442</ref> <ref>PMID:16603527</ref> <ref>PMID:16775318</ref> <ref>PMID:20862315</ref> <ref>PMID:20202662</ref>	+	[https://www.uniprot.org/uniprot/VGP_EBOZM VGP_EBOZM] GP1 is responsible for binding to the receptor(s) on target cells. Interacts with CD209/DC-SIGN and CLEC4M/DC-SIGNR which act as cofactors for virus entry into the host cell. Binding to CD209 and CLEC4M, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses, facilitate infection of macrophages and endothelial cells. These interactions not only facilitate virus cell entry, but also allow capture of viral particles by DCs and subsequent transmission to susceptible cells without DCs infection (trans infection). Binding to the macrophage specific lectin CLEC10A also seem to enhance virus infectivity. Interaction with FOLR1/folate receptor alpha may be a cofactor for virus entry in some cell types, although results are contradictory. Members of the Tyro3 receptor tyrosine kinase family also seem to be cell entry factors in filovirus infection. Once attached, the virions are internalized through clathrin-dependent endocytosis and/or macropinocytosis. After internalization of the virus into the endosomes of the host cell, proteolysis of GP1 by two cysteine proteases, CTSB/cathepsin B and CTSL/cathepsin L presumably induces a conformational change of GP2, unmasking its fusion peptide and initiating membranes fusion.<ref>PMID:10932225</ref> <ref>PMID:12050398</ref> <ref>PMID:16051836</ref> <ref>PMID:15681442</ref> <ref>PMID:16603527</ref> <ref>PMID:16775318</ref> <ref>PMID:20862315</ref> <ref>PMID:20202662</ref> GP2 acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in GP2, releasing the fusion hydrophobic peptide.<ref>PMID:10932225</ref> <ref>PMID:12050398</ref> <ref>PMID:16051836</ref> <ref>PMID:15681442</ref> <ref>PMID:16603527</ref> <ref>PMID:16775318</ref> <ref>PMID:20862315</ref> <ref>PMID:20202662</ref> GP1,2 mediates endothelial cell activation and decreases endothelial barrier function. Mediates activation of primary macrophages. At terminal stages of the viral infection, when its expression is high, GP1,2 down-modulates the expression of various host cell surface molecules that are essential for immune surveillance and cell adhesion. Down-modulates integrins ITGA1, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGAV and ITGB1. GP1,2 alters the cellular recycling of the dimer alpha-V/beta-3 via a dynamin-dependent pathway. Decrease in the host cell surface expression of various adhesion molecules may lead to cell detachment, contributing to the disruption of blood vessel integrity and hemorrhages developed during Ebola virus infection (cytotoxicity). This cytotoxicity appears late in the infection, only after the massive release of viral particles by infected cells. Down-modulation of host MHC-I, leading to altered recognition by immune cells, may explain the immune suppression and inflammatory dysfunction linked to Ebola infection. Also down-modulates EGFR surface expression.<ref>PMID:10932225</ref> <ref>PMID:12050398</ref> <ref>PMID:16051836</ref> <ref>PMID:15681442</ref> <ref>PMID:16603527</ref> <ref>PMID:16775318</ref> <ref>PMID:20862315</ref> <ref>PMID:20202662</ref> GP2delta is part of the complex GP1,2delta released by host ADAM17 metalloprotease. This secreted complex may play a role in the pathogenesis of the virus by efficiently blocking the neutralizing antibodies that would otherwise neutralize the virus surface glycoproteins GP1,2. Might therefore contribute to the lack of inflammatory reaction seen during infection in spite the of extensive necrosis and massive virus production. GP1,2delta does not seem to be involved in activation of primary macrophages.<ref>PMID:10932225</ref> <ref>PMID:12050398</ref> <ref>PMID:16051836</ref> <ref>PMID:15681442</ref> <ref>PMID:16603527</ref> <ref>PMID:16775318</ref> <ref>PMID:20862315</ref> <ref>PMID:20202662</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 26:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Crab~~-~~eating macaque]]~~	+	[[Category: Ebola virus - Mayinga, Zaire, 1976]]
-	~~[[Category: Ebov-may~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Janus, B M~~]]	+	[[Category: Macaca fascicularis]]
-	[[Category: ~~Ofek, G~~]]	+	[[Category: Janus BM]]
-	[[Category: ~~Broadly neutralizing antibody]]~~	+	[[Category: Ofek G]]
-	~~[[Category: Ca45]]~~	+
-	~~[[Category: Cross-protective antibody]]~~	+
-	~~[[Category: Cross-reactive]]~~	+
-	~~[[Category: Ebolavirus]]~~	+
-	~~[[Category: Filovirus]]~~	+
-	~~[[Category: Fusion loop]]~~	+
-	~~[[Category: Glycoprotein]]~~	+
-	~~[[Category: Viral protein~~]]	+

OCA at 09:10, 11 November 2020

OCA — Wed, 11 Nov 2020 09:10:32 GMT

←Older revision		Revision as of 09:10, 11 November 2020
Line 1:		Line 1:

	==Structural Basis for Broad Neutralization of Ebolaviruses by an Antibody Targeting the Glycoprotein Fusion Loop==		==Structural Basis for Broad Neutralization of Ebolaviruses by an Antibody Targeting the Glycoprotein Fusion Loop==
-	<StructureSection load='6eay' size='340' side='right' caption='[[6eay]], [[Resolution\|resolution]] 3.72Å' scene=''>	+	<StructureSection load='6eay' size='340' side='right'caption='[[6eay]], [[Resolution\|resolution]] 3.72Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6eay]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EAY OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6EAY FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6eay]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Crab-eating_macaque Crab-eating macaque] and [http://en.wikipedia.org/wiki/Ebov-may Ebov-may]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EAY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6EAY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=~~MAN~~:~~ALPHA~~-D-~~MANNOSE~~'>~~MAN~~</scene>, <scene name='pdbligand=~~NAG~~:~~N-ACETYL~~-D-~~GLUCOSAMINE~~'>~~NAG~~</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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=6eay FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eay OCA], [http://pdbe.org/6eay PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eay RCSB], [http://www.ebi.ac.uk/pdbsum/6eay PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eay ProSAT]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=128952 EBOV-May])</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=6eay FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eay OCA], [http://pdbe.org/6eay PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eay RCSB], [http://www.ebi.ac.uk/pdbsum/6eay PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eay ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6eay" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6eay" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Glycoprotein GP 3D structures\|Glycoprotein GP 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Crab-eating macaque]]
		+	[[Category: Ebov-may]]
		+	[[Category: Large Structures]]
	[[Category: Janus, B M]]		[[Category: Janus, B M]]
	[[Category: Ofek, G]]		[[Category: Ofek, G]]

OCA at 08:08, 10 October 2018

OCA — Wed, 10 Oct 2018 08:08:12 GMT

←Older revision		Revision as of 08:08, 10 October 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6eay is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Structural Basis for Broad Neutralization of Ebolaviruses by an Antibody Targeting the Glycoprotein Fusion Loop==
		+	<StructureSection load='6eay' size='340' side='right' caption='[[6eay]], [[Resolution\|resolution]] 3.72Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6eay]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EAY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EAY FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=6eay FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eay OCA], [http://pdbe.org/6eay PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eay RCSB], [http://www.ebi.ac.uk/pdbsum/6eay PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eay ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/VGP_EBOZM VGP_EBOZM]] GP1 is responsible for binding to the receptor(s) on target cells. Interacts with CD209/DC-SIGN and CLEC4M/DC-SIGNR which act as cofactors for virus entry into the host cell. Binding to CD209 and CLEC4M, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses, facilitate infection of macrophages and endothelial cells. These interactions not only facilitate virus cell entry, but also allow capture of viral particles by DCs and subsequent transmission to susceptible cells without DCs infection (trans infection). Binding to the macrophage specific lectin CLEC10A also seem to enhance virus infectivity. Interaction with FOLR1/folate receptor alpha may be a cofactor for virus entry in some cell types, although results are contradictory. Members of the Tyro3 receptor tyrosine kinase family also seem to be cell entry factors in filovirus infection. Once attached, the virions are internalized through clathrin-dependent endocytosis and/or macropinocytosis. After internalization of the virus into the endosomes of the host cell, proteolysis of GP1 by two cysteine proteases, CTSB/cathepsin B and CTSL/cathepsin L presumably induces a conformational change of GP2, unmasking its fusion peptide and initiating membranes fusion.<ref>PMID:10932225</ref> <ref>PMID:12050398</ref> <ref>PMID:16051836</ref> <ref>PMID:15681442</ref> <ref>PMID:16603527</ref> <ref>PMID:16775318</ref> <ref>PMID:20862315</ref> <ref>PMID:20202662</ref> GP2 acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in GP2, releasing the fusion hydrophobic peptide.<ref>PMID:10932225</ref> <ref>PMID:12050398</ref> <ref>PMID:16051836</ref> <ref>PMID:15681442</ref> <ref>PMID:16603527</ref> <ref>PMID:16775318</ref> <ref>PMID:20862315</ref> <ref>PMID:20202662</ref> GP1,2 mediates endothelial cell activation and decreases endothelial barrier function. Mediates activation of primary macrophages. At terminal stages of the viral infection, when its expression is high, GP1,2 down-modulates the expression of various host cell surface molecules that are essential for immune surveillance and cell adhesion. Down-modulates integrins ITGA1, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGAV and ITGB1. GP1,2 alters the cellular recycling of the dimer alpha-V/beta-3 via a dynamin-dependent pathway. Decrease in the host cell surface expression of various adhesion molecules may lead to cell detachment, contributing to the disruption of blood vessel integrity and hemorrhages developed during Ebola virus infection (cytotoxicity). This cytotoxicity appears late in the infection, only after the massive release of viral particles by infected cells. Down-modulation of host MHC-I, leading to altered recognition by immune cells, may explain the immune suppression and inflammatory dysfunction linked to Ebola infection. Also down-modulates EGFR surface expression.<ref>PMID:10932225</ref> <ref>PMID:12050398</ref> <ref>PMID:16051836</ref> <ref>PMID:15681442</ref> <ref>PMID:16603527</ref> <ref>PMID:16775318</ref> <ref>PMID:20862315</ref> <ref>PMID:20202662</ref> GP2delta is part of the complex GP1,2delta released by host ADAM17 metalloprotease. This secreted complex may play a role in the pathogenesis of the virus by efficiently blocking the neutralizing antibodies that would otherwise neutralize the virus surface glycoproteins GP1,2. Might therefore contribute to the lack of inflammatory reaction seen during infection in spite the of extensive necrosis and massive virus production. GP1,2delta does not seem to be involved in activation of primary macrophages.<ref>PMID:10932225</ref> <ref>PMID:12050398</ref> <ref>PMID:16051836</ref> <ref>PMID:15681442</ref> <ref>PMID:16603527</ref> <ref>PMID:16775318</ref> <ref>PMID:20862315</ref> <ref>PMID:20202662</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The severity of the 2014-2016 ebolavirus outbreak in West Africa expedited clinical development of therapeutics and vaccines though the countermeasures on hand were largely monospecific and lacked efficacy against other ebolavirus species that previously emerged. Recent studies indicate that ebolavirus glycoprotein (GP) fusion loops are targets for cross-protective antibodies. Here we report the 3.72 A resolution crystal structure of one such cross-protective antibody, CA45, bound to the ectodomain of Ebola virus (EBOV) GP. The CA45 epitope spans multiple faces of the fusion loop stem, across both GP1 and GP2 subunits, with ~68% of residues identical across > 99.5% of known ebolavirus isolates. Extensive antibody interactions within a pan-ebolavirus small-molecule inhibitor binding cavity on GP define this cavity as a novel site of immune vulnerability. The structure elucidates broad ebolavirus neutralization through a highly conserved epitope on GP and further enables rational design and development of broadly protective vaccines and therapeutics.

-	~~Authors~~:	+	Structural basis for broad neutralization of ebolaviruses by an antibody targeting the glycoprotein fusion loop.,Janus BM, van Dyk N, Zhao X, Howell KA, Soto C, Aman MJ, Li Y, Fuerst TR, Ofek G Nat Commun. 2018 Sep 26;9(1):3934. doi: 10.1038/s41467-018-06113-4. PMID:30258051<ref>PMID:30258051</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6eay" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Janus, B M]]
		+	[[Category: Ofek, G]]
		+	[[Category: Broadly neutralizing antibody]]
		+	[[Category: Ca45]]
		+	[[Category: Cross-protective antibody]]
		+	[[Category: Cross-reactive]]
		+	[[Category: Ebolavirus]]
		+	[[Category: Filovirus]]
		+	[[Category: Fusion loop]]
		+	[[Category: Glycoprotein]]
		+	[[Category: Viral protein]]

OCA at 18:04, 19 September 2018

OCA — Wed, 19 Sep 2018 18:04:33 GMT

←Older revision		Revision as of 18:04, 19 September 2018
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

OCA at 08:41, 5 September 2018

OCA — Wed, 05 Sep 2018 08:41:14 GMT

←Older revision		Revision as of 08:41, 5 September 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6eay is ON HOLD ~~until Paper Publication~~	+	The entry 6eay is ON HOLD

	Authors:		Authors:

OCA at 05:42, 29 August 2018

OCA — Wed, 29 Aug 2018 05:42:51 GMT

←Older revision		Revision as of 05:42, 29 August 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 15 Aug 2018 14:48:19 GMT

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

←Older revision

Revision as of 14:48, 15 August 2018

OCA: New page: '''Unreleased structure''' The entry 6eay is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 15 Aug 2018 14:48:18 GMT

New page: '''Unreleased structure''' The entry 6eay is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6eay is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]