5npi - Revision history

OCA at 13:19, 15 November 2023

OCA — Wed, 15 Nov 2023 13:19:45 GMT

←Older revision		Revision as of 13:19, 15 November 2023
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	<StructureSection load='5npi' size='340' side='right'caption='[[5npi]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='5npi' size='340' side='right'caption='[[5npi]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5npi]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Lk3_transgenic_mice Lk3 transgenic mice~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NPI OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5NPI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5npi]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepacivirus_C Hepacivirus C] 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=5NPI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NPI 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=5npi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5npi OCA], [~~http~~://pdbe.org/5npi PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5npi RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5npi PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5npi 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]] 2Å</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=5npi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5npi OCA], [https://pdbe.org/5npi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5npi RCSB], [https://www.ebi.ac.uk/pdbsum/5npi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5npi ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/POLG_HCVJ4 POLG_HCVJ4] Core protein packages viral RNA to form a viral nucleocapsid, and promotes virion budding. Modulates viral translation initiation by interacting with HCV IRES and 40S ribosomal subunit. Also regulates many host cellular functions such as signaling pathways and apoptosis. Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways and by inducing human STAT1 degradation. Thought to play a role in virus-mediated cell transformation leading to hepatocellular carcinomas. Interacts with, and activates STAT3 leading to cellular transformation. May repress the promoter of p53, and sequester CREB3 and SP110 isoform 3/Sp110b in the cytoplasm. Also represses cell cycle negative regulating factor CDKN1A, thereby interrupting an important check point of normal cell cycle regulation. Targets transcription factors involved in the regulation of inflammatory responses and in the immune response: suppresses NK-kappaB activation, and activates AP-1. Could mediate apoptotic pathways through association with TNF-type receptors TNFRSF1A and LTBR, although its effect on death receptor-induced apoptosis remains controversial. Enhances TRAIL mediated apoptosis, suggesting that it might play a role in immune-mediated liver cell injury. Seric core protein is able to bind C1QR1 at the T-cell surface, resulting in down-regulation of T-lymphocytes proliferation. May transactivate human MYC, Rous sarcoma virus LTR, and SV40 promoters. May suppress the human FOS and HIV-1 LTR activity. Alters lipid metabolism by interacting with hepatocellular proteins involved in lipid accumulation and storage. Core protein induces up-regulation of FAS promoter activity, and thereby probably contributes to the increased triglyceride accumulation in hepatocytes (steatosis) (By similarity). E1 and E2 glycoproteins form a heterodimer that is involved in virus attachment to the host cell, virion internalization through clathrin-dependent endocytosis and fusion with host membrane. E1/E2 heterodimer binds to human LDLR, CD81 and SCARB1/SR-BI receptors, but this binding is not sufficient for infection, some additional liver specific cofactors may be needed. The fusion function may possibly be carried by E1. E2 inhibits human EIF2AK2/PKR activation, preventing the establishment of an antiviral state. E2 is a viral ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on liver sinusoidal endothelial cells and macrophage-like cells of lymph node sinuses. These interactions allow capture of circulating HCV particles by these cells and subsequent transmission to permissive cells. DCs act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. Capture of circulating HCV particles by these SIGN+ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection (By similarity). P7 seems to be a heptameric ion channel protein (viroporin) and is inhibited by the antiviral drug amantadine. Also inhibited by long-alkyl-chain iminosugar derivatives. Essential for infectivity (By similarity). Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity). NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS4A, is responsible for the cleavages of NS3-NS4A, NS4A-NS4B, NS4B-NS5A and NS5A-NS5B. NS3/NS4A complex also prevents phosphorylation of human IRF3, thus preventing the establishment of dsRNA induced antiviral state. NS3 RNA helicase binds to RNA and unwinds dsRNA in the 3' to 5' direction, and likely RNA stable secondary structure in the template strand. Cleaves and inhibits the host antiviral protein MAVS (By similarity). NS4B induces a specific membrane alteration that serves as a scaffold for the virus replication complex. This membrane alteration gives rise to the so-called ER-derived membranous web that contains the replication complex (By similarity). NS5A is a component of the replication complex involved in RNA-binding. Its interaction with Human VAPB may target the viral replication complex to vesicles. Down-regulates viral IRES translation initiation. Mediates interferon resistance, presumably by interacting with and inhibiting human EIF2AK2/PKR. Seems to inhibit apoptosis by interacting with BIN1 and FKBP8. The hyperphosphorylated form of NS5A is an inhibitor of viral replication (By similarity). NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Hepacivirus C]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Lk3 transgenic mice~~]]	+	[[Category: Mus musculus]]
-	[[Category: Krey, T]]	+	[[Category: Krey T]]
-	[[Category: Rey~~, F A~~]]	+	[[Category: Rey FA]]
-	[[Category: Vasiliauskaite, I]]	+	[[Category: Vasiliauskaite I]]
-	~~[[Category: Cd81 binding loop]]~~	+
-	~~[[Category: Envelope glycoprotein]]~~	+
-	~~[[Category: Hepatitis c virus]]~~	+
-	~~[[Category: Single chain variable fragment]]~~	+
-	~~[[Category: Viral protein~~]]	+

OCA at 12:09, 26 August 2020

OCA — Wed, 26 Aug 2020 12:09:47 GMT

←Older revision		Revision as of 12:09, 26 August 2020
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	==Structure of the Hepatitis C virus strain J4 glycoprotein E2 antigenic region 532-540 bound to the single chain variable fragment of the non-neutralizing antibody DAO5==		==Structure of the Hepatitis C virus strain J4 glycoprotein E2 antigenic region 532-540 bound to the single chain variable fragment of the non-neutralizing antibody DAO5==
-	<StructureSection load='5npi' size='340' side='right' caption='[[5npi]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='5npi' size='340' side='right'caption='[[5npi]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5npi]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NPI OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5NPI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5npi]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NPI OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5NPI 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=5npi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5npi OCA], [http://pdbe.org/5npi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5npi RCSB], [http://www.ebi.ac.uk/pdbsum/5npi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5npi 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=5npi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5npi OCA], [http://pdbe.org/5npi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5npi RCSB], [http://www.ebi.ac.uk/pdbsum/5npi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5npi ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
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	</div>		</div>
	<div class="pdbe-citations 5npi" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5npi" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Antibody 3D structures\|Antibody 3D structures]]
		+	*[[3D structures of non-human antibody\|3D structures of non-human antibody]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Lk3 transgenic mice]]
	[[Category: Krey, T]]		[[Category: Krey, T]]
	[[Category: Rey, F A]]		[[Category: Rey, F A]]

OCA at 13:41, 24 May 2017

OCA — Wed, 24 May 2017 13:41:18 GMT

←Older revision		Revision as of 13:41, 24 May 2017
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-	'''Unreleased structure'''

-	The entry ~~5npi~~ is ~~ON HOLD~~	+	==Structure of the Hepatitis C virus strain J4 glycoprotein E2 antigenic region 532-540 bound to the single chain variable fragment of the non-neutralizing antibody DAO5==
		+	<StructureSection load='5npi' size='340' side='right' caption='[[5npi]], [[Resolution\|resolution]] 2.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5npi]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NPI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NPI 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=5npi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5npi OCA], [http://pdbe.org/5npi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5npi RCSB], [http://www.ebi.ac.uk/pdbsum/5npi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5npi ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The hepatitis C virus (HCV) glycoprotein E2 is the major target of neutralizing antibodies and is therefore highly relevant for vaccine design. Its structure features a central immunoglobulin (Ig)-like beta-sandwich that contributes to the binding site for the cellular receptor CD81. We show that a synthetic peptide corresponding to a beta-strand of this Ig-like domain forms an alpha-helix in complex with the anti-E2 antibody DAO5, demonstrating an inside-out flip of hydrophobic residues and a secondary structure change in the composite CD81 binding site. A detailed interaction analysis of DAO5 and cross-competing neutralizing antibodies with soluble E2 revealed that the Ig-like domain is trapped by different antibodies in at least two distinct conformations. DAO5 specifically captures retrovirus particles bearing HCV glycoproteins (HCVpp) and infectious cell culture-derived HCV particles (HCVcc). Infection of cells by DAO5-captured HCVpp can be blocked by a cross-competing neutralizing antibody, indicating that a single virus particle simultaneously displays E2 molecules in more than one conformation on its surface. Such conformational plasticity of the HCV E2 receptor binding site has important implications for immunogen design.IMPORTANCE Recent advances in the treatment of hepatitis C virus (HCV) infection with direct-acting antiviral drugs have enabled the control of this major human pathogen. However, due to their high costs and limited accessibility in combination with the lack of awareness of the mostly asymptomatic infection, there is an unchanged urgent need for an effective vaccine. The viral glycoprotein E2 contains regions that are crucial for virus entry into the host cell, and antibodies that bind to these regions can neutralize infection. One of the major targets of neutralizing antibodies is the central immunoglobulin (Ig)-like domain within E2. We show here that this Ig-like domain is conformationally flexible at the surface of infectious HCV particles and pseudoparticles. Our study provides novel insights into the interactions of HCV E2 with the humoral immune system that should aid future vaccine development.

-	~~Authors: Vasiliauskaite~~, I., Rey, ~~F.A.~~, Krey, T.	+	Conformational Flexibility in the Immunoglobulin-Like Domain of the Hepatitis C Virus Glycoprotein E2.,Vasiliauskaite I, Owsianka A, England P, Khan AG, Cole S, Bankwitz D, Foung SKH, Pietschmann T, Marcotrigiano J, Rey FA, Patel AH, Krey T MBio. 2017 May 16;8(3). pii: e00382-17. doi: 10.1128/mBio.00382-17. PMID:28512091<ref>PMID:28512091</ref>

-	~~Description: Structure~~ of the ~~Hepatitis C virus strain J4 glycoprotein E2 antigenic region 532-540 bound to the single chain variable fragment~~ of ~~the non-neutralizing antibody DAO5~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Rey, F.A]]~~	+	<div class="pdbe-citations 5npi" style="background-color:#fffaf0;"></div>
-	~~[[Category: Vasiliauskaite, I]]~~	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Krey, T]]		[[Category: Krey, T]]
		+	[[Category: Rey, F A]]
		+	[[Category: Vasiliauskaite, I]]
		+	[[Category: Cd81 binding loop]]
		+	[[Category: Envelope glycoprotein]]
		+	[[Category: Hepatitis c virus]]
		+	[[Category: Single chain variable fragment]]
		+	[[Category: Viral protein]]

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

OCA — Thu, 27 Apr 2017 10:45:03 GMT

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

←Older revision

Revision as of 10:45, 27 April 2017

OCA: New page: '''Unreleased structure''' The entry 5npi is ON HOLD Authors: Vasiliauskaite, I., Rey, F.A., Krey, T. Description: Structure of the Hepatitis C virus strain J4 glycoprotein E2 antigeni...

OCA — Thu, 27 Apr 2017 10:45:01 GMT

New page: '''Unreleased structure''' The entry 5npi is ON HOLD Authors: Vasiliauskaite, I., Rey, F.A., Krey, T. Description: Structure of the Hepatitis C virus strain J4 glycoprotein E2 antigeni...

New page

'''Unreleased structure'''

The entry 5npi is ON HOLD

Authors: Vasiliauskaite, I., Rey, F.A., Krey, T.

Description: Structure of the Hepatitis C virus strain J4 glycoprotein E2 antigenic region 532-540 bound to the single chain variable fragment of the non-neutralizing antibody DAO5
[[Category: Unreleased Structures]]
[[Category: Rey, F.A]]
[[Category: Vasiliauskaite, I]]
[[Category: Krey, T]]