2y6s - Revision history

OCA at 10:46, 20 December 2023

OCA — Wed, 20 Dec 2023 10:46:49 GMT

←Older revision		Revision as of 10:46, 20 December 2023
Line 3:		Line 3:
	<StructureSection load='2y6s' size='340' side='right'caption='[[2y6s]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='2y6s' size='340' side='right'caption='[[2y6s]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2y6s]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y6S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Y6S FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2y6s]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Ebola_virus_-_Zaire_(1995) Ebola virus - Zaire (1995)] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y6S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Y6S FirstGlance]. <br>
-	</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=2y6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y6s OCA], [https://pdbe.org/2y6s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2y6s RCSB], [https://www.ebi.ac.uk/pdbsum/2y6s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2y6s ProSAT]</span></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]] 2.8Å</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=2y6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y6s OCA], [https://pdbe.org/2y6s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2y6s RCSB], [https://www.ebi.ac.uk/pdbsum/2y6s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2y6s ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/VGP_EBOZ5 VGP_EBOZ5]] 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 seems 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 (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity).	+	[https://www.uniprot.org/uniprot/VGP_EBOZ5 VGP_EBOZ5] 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 seems 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 (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 24:
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Mus musculus]]		[[Category: Mus musculus]]
-	[[Category: Bale, S]]	+	[[Category: Bale S]]
-	[[Category: Dye~~, J M~~]]	+	[[Category: Dye JM]]
-	[[Category: Kuehne, A]]	+	[[Category: Kuehne A]]
-	[[Category: Lee~~, J E~~]]	+	[[Category: Lee JE]]
-	[[Category: Olal~~, D O~~]]	+	[[Category: Olal DO]]
-	[[Category: Saphire~~, E O]]~~	+	[[Category: Saphire EO]]
-	~~[[Category: Immune system-viral protein complex~~]]	+

OCA at 12:24, 27 April 2022

OCA — Wed, 27 Apr 2022 12:24:12 GMT

←Older revision		Revision as of 12:24, 27 April 2022
Line 3:		Line 3:
	<StructureSection load='2y6s' size='340' side='right'caption='[[2y6s]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='2y6s' size='340' side='right'caption='[[2y6s]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2y6s]] is a 6 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y6S OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=2Y6S FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2y6s]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y6S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Y6S 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=2y6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y6s OCA], [~~http~~://pdbe.org/2y6s PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2y6s RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2y6s PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2y6s ProSAT]</span></td></tr>	+	</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=2y6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y6s OCA], [https://pdbe.org/2y6s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2y6s RCSB], [https://www.ebi.ac.uk/pdbsum/2y6s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2y6s ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/VGP_EBOZ5 VGP_EBOZ5]] 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 seems 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 (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity).	+	[[https://www.uniprot.org/uniprot/VGP_EBOZ5 VGP_EBOZ5]] 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 seems 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 (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 12:37, 22 July 2020

OCA — Wed, 22 Jul 2020 12:37:08 GMT

←Older revision		Revision as of 12:37, 22 July 2020
Line 1:		Line 1:

	==Structure of an Ebolavirus-protective antibody in complex with its mucin-domain linear epitope==		==Structure of an Ebolavirus-protective antibody in complex with its mucin-domain linear epitope==
-	<StructureSection load='2y6s' size='340' side='right' caption='[[2y6s]], [[Resolution\|resolution]] 2.80Å' scene=''>	+	<StructureSection load='2y6s' size='340' side='right'caption='[[2y6s]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2y6s]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y6S OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2Y6S FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2y6s]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y6S OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2Y6S 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=2y6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y6s OCA], [http://pdbe.org/2y6s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2y6s RCSB], [http://www.ebi.ac.uk/pdbsum/2y6s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2y6s 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=2y6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y6s OCA], [http://pdbe.org/2y6s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2y6s RCSB], [http://www.ebi.ac.uk/pdbsum/2y6s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2y6s ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 21:		Line 21:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Mus musculus]]		[[Category: Mus musculus]]
	[[Category: Bale, S]]		[[Category: Bale, S]]

OCA at 21:23, 5 August 2016

OCA — Fri, 05 Aug 2016 21:23:04 GMT

←Older revision		Revision as of 21:23, 5 August 2016
Line 1:		Line 1:
		+
	==Structure of an Ebolavirus-protective antibody in complex with its mucin-domain linear epitope==		==Structure of an Ebolavirus-protective antibody in complex with its mucin-domain linear epitope==
	<StructureSection load='2y6s' size='340' side='right' caption='[[2y6s]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='2y6s' size='340' side='right' caption='[[2y6s]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2y6s]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y6S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Y6S FirstGlance]. <br>		<table><tr><td colspan='2'>[[2y6s]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y6S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Y6S 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=2y6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y6s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2y6s RCSB], [http://www.ebi.ac.uk/pdbsum/2y6s PDBsum]</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=2y6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y6s OCA], [http://pdbe.org/2y6s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2y6s RCSB], [http://www.ebi.ac.uk/pdbsum/2y6s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2y6s ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 15:		Line 16:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 2y6s" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 22:00, 25 December 2014

OCA — Thu, 25 Dec 2014 22:00:24 GMT

←Older revision		Revision as of 22:00, 25 December 2014
Line 2:		Line 2:
	<StructureSection load='2y6s' size='340' side='right' caption='[[2y6s]], [[Resolution\|resolution]] 2.80Å' scene=''>		<StructureSection load='2y6s' size='340' side='right' caption='[[2y6s]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2y6s]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y6S OCA]. ~~<br>~~	+	<table><tr><td colspan='2'>[[2y6s]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y6S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Y6S FirstGlance]. <br>
-	~~</td></tr><tr><td class="sblockLbl">~~<b>~~Activity:~~</b>~~</td><td class="sblockDat"><span class='plainlinks'>~~[http://en.~~wikipedia~~.~~org/wiki/Glucokinase Glucokinase], with EC number [http:~~/~~/www.brenda~~-~~enzymes.info~~/~~php~~/~~result_flat~~.~~php4~~?~~ecno~~=2.~~7.1.2 2.7.1.2]~~ <~~/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=2y6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y6s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2y6s RCSB], [http://www.ebi.ac.uk/pdbsum/2y6s PDBsum]</span></td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2y6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y6s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2y6s RCSB], [http://www.ebi.ac.uk/pdbsum/2y6s PDBsum]</span></td></tr>	+	</table>
-	<table>	+	== Function ==
		+	[[http://www.uniprot.org/uniprot/VGP_EBOZ5 VGP_EBOZ5]] 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 seems 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 (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 12:		Line 13:
	Structure of an Ebola virus-protective antibody in complex with its mucin-domain linear epitope.,Olal D, Kuehne A, Bale S, Halfmann P, Hashiguchi T, Fusco ML, Lee JE, King LB, Kawaoka Y, Dye JM Jr, Saphire EO J Virol. 2011 Dec 14. PMID:22171276<ref>PMID:22171276</ref>		Structure of an Ebola virus-protective antibody in complex with its mucin-domain linear epitope.,Olal D, Kuehne A, Bale S, Halfmann P, Hashiguchi T, Fusco ML, Lee JE, King LB, Kawaoka Y, Dye JM Jr, Saphire EO J Virol. 2011 Dec 14. PMID:22171276<ref>PMID:22171276</ref>

-	From ~~MEDLINEÂ®~~/~~PubMedÂ®~~, a database of the U.S. National Library of Medicine.<br>	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
	== References ==		== References ==
Line 19:		Line 20:
	</StructureSection>		</StructureSection>
	[[Category: Mus musculus]]		[[Category: Mus musculus]]
-	[[Category: Bale, S.]]	+	[[Category: Bale, S]]
-	[[Category: Dye, J M.]]	+	[[Category: Dye, J M]]
-	[[Category: Kuehne, A.]]	+	[[Category: Kuehne, A]]
-	[[Category: Lee, J E.]]	+	[[Category: Lee, J E]]
-	[[Category: Olal, D O.]]	+	[[Category: Olal, D O]]
-	[[Category: Saphire, E O.]]	+	[[Category: Saphire, E O]]
	[[Category: Immune system-viral protein complex]]		[[Category: Immune system-viral protein complex]]

OCA at 07:49, 14 May 2014

OCA — Wed, 14 May 2014 07:49:10 GMT

←Older revision		Revision as of 07:49, 14 May 2014
Line 1:		Line 1:
-	[[~~Image~~:2y6s.~~png\|left\|200px~~]]	+	==Structure of an Ebolavirus-protective antibody in complex with its mucin-domain linear epitope==
		+	<StructureSection load='2y6s' size='340' side='right' caption='[[2y6s]], [[Resolution\|resolution]] 2.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2y6s]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y6S OCA]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2y6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y6s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2y6s RCSB], [http://www.ebi.ac.uk/pdbsum/2y6s PDBsum]</span></td></tr>
		+	<table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Antibody 14G7 is protective against lethal Ebola virus challenge, and recognizes a distinct linear epitope in the prominent mucin-like domain of the Ebola virus glycoprotein GP. The structure of 14G7 in complex with its linear peptide epitope has now been determined to 2.8 A. The structure shows that this GP sequence forms a tandem ss hairpin structure that binds deeply into a cleft in the antibody-combining site. A key threonine at the apex of one turn is critical for antibody interaction and is conserved among all ebolaviruses. This work provides further insight into the mechanism of protection by antibodies that target the protruding, highly accessible mucin-like domain of Ebola virus and the structural framework for understanding and characterizing candidate immunotherapeutics.

-	<!--	+	Structure of an Ebola virus-protective antibody in complex with its mucin-domain linear epitope.,Olal D, Kuehne A, Bale S, Halfmann P, Hashiguchi T, Fusco ML, Lee JE, King LB, Kawaoka Y, Dye JM Jr, Saphire EO J Virol. 2011 Dec 14. PMID:22171276<ref>PMID:22171276</ref>
-	~~The line below this paragraph~~, ~~containing "STRUCTURE_2y6s"~~, ~~creates the "Structure Box" on the page.~~	+
-	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~	+
-	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded)~~,	+
-	~~or leave the SCENE parameter empty for the default display~~.	+
-	-->	+
-	~~{{STRUCTURE_2y6s\| PDB=2y6s \| SCENE= }}~~	+

-	~~===Structure~~ of ~~an Ebolavirus-protective antibody in complex with its mucin-domain linear epitope===~~	+	From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-		+	== References ==
-	~~<!--~~	+	<references/>
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_22171276}}, adds~~ the ~~Publication Abstract to the page~~	+	__TOC__
-	~~(as it appears on PubMed at http://www~~.~~pubmed~~.~~gov), where 22171276 is the PubMed ID number~~.	+	</StructureSection>
-	-->	+
-	~~{{ABSTRACT_PUBMED_22171276}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[2y6s]] is a 6 chain structure with sequence from [http:~~/~~/en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y6S OCA].~~	+
-		+
-	==~~Reference~~==	+
-	<~~ref group="xtra">PMID:022171276<~~/~~ref~~><~~references group="xtra"~~/>	+
	[[Category: Mus musculus]]		[[Category: Mus musculus]]
	[[Category: Bale, S.]]		[[Category: Bale, S.]]

OCA at 06:18, 11 January 2012

OCA — Wed, 11 Jan 2012 06:18:06 GMT

←Older revision		Revision as of 06:18, 11 January 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:2y6s.png\|left\|200px]]

-	The ~~entry 2y6s~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_2y6s", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_2y6s\| PDB=2y6s \| SCENE= }}

-	~~Authors: Olal, D.O., Kuehne, A., Lee, J., Bale, S., Dye, J.M., Saphire, E.O.~~	+	===Structure of an Ebolavirus-protective antibody in complex with its mucin-domain linear epitope===

-	~~Description~~: ~~Structure of an Ebolavirus~~-~~protective antibody in complex~~ with ~~its mucin~~-~~domain linear epitope~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_22171276}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 22171276 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_22171276}}
		+
		+	==About this Structure==
		+	[[2y6s]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y6S OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022171276</ref><references group="xtra"/>
		+	[[Category: Mus musculus]]
		+	[[Category: Bale, S.]]
		+	[[Category: Dye, J M.]]
		+	[[Category: Kuehne, A.]]
		+	[[Category: Lee, J E.]]
		+	[[Category: Olal, D O.]]
		+	[[Category: Saphire, E O.]]
		+	[[Category: Immune system-viral protein complex]]

OCA at 06:19, 4 May 2011

OCA — Wed, 04 May 2011 06:19:22 GMT

←Older revision		Revision as of 06:19, 4 May 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 2y6s is ON HOLD	+	The entry 2y6s is ON HOLD until Paper Publication

	Authors: Olal, D.O., Kuehne, A., Lee, J., Bale, S., Dye, J.M., Saphire, E.O.		Authors: Olal, D.O., Kuehne, A., Lee, J., Bale, S., Dye, J.M., Saphire, E.O.

	Description: Structure of an Ebolavirus-protective antibody in complex with its mucin-domain linear epitope		Description: Structure of an Ebolavirus-protective antibody in complex with its mucin-domain linear epitope

OCA: Protected "2y6s" [edit=sysop:move=sysop]

OCA — Wed, 02 Feb 2011 06:01:40 GMT

Protected "2y6s" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:01, 2 February 2011

OCA: New page: '''Unreleased structure''' The entry 2y6s is ON HOLD Authors: Olal, D.O., Kuehne, A., Lee, J., Bale, S., Dye, J.M., Saphire, E.O. Description: Structure of an Ebolavirus-protective ant...

OCA — Wed, 02 Feb 2011 06:01:39 GMT

New page: '''Unreleased structure''' The entry 2y6s is ON HOLD Authors: Olal, D.O., Kuehne, A., Lee, J., Bale, S., Dye, J.M., Saphire, E.O. Description: Structure of an Ebolavirus-protective ant...

New page

'''Unreleased structure'''

The entry 2y6s is ON HOLD

Authors: Olal, D.O., Kuehne, A., Lee, J., Bale, S., Dye, J.M., Saphire, E.O.

Description: Structure of an Ebolavirus-protective antibody in complex with its mucin-domain linear epitope