5kzp - Revision history

OCA at 16:03, 4 October 2023

OCA — Wed, 04 Oct 2023 16:03:28 GMT

←Older revision		Revision as of 16:03, 4 October 2023
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	<StructureSection load='5kzp' size='340' side='right'caption='[[5kzp]], [[Resolution\|resolution]] 2.26Å' scene=''>		<StructureSection load='5kzp' size='340' side='right'caption='[[5kzp]], [[Resolution\|resolution]] 2.26Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5kzp]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KZP OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5KZP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5kzp]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepacivirus_C Hepacivirus C] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KZP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KZP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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]] 2.262Å</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=5kzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kzp OCA], [~~http~~://pdbe.org/5kzp PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5kzp RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5kzp PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5kzp ProSAT]</span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></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=5kzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kzp OCA], [https://pdbe.org/5kzp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kzp RCSB], [https://www.ebi.ac.uk/pdbsum/5kzp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kzp ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/POLG_HCVBK POLG_HCVBK] 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> Protease NS2-3 is a cysteine protease responsible for the autocatalytic cleavage of NS2-NS3. Seems to undergo self-inactivation following maturation (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> 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).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref> NS5B is a RNA-dependent RNA polymerase that plays an essential role in the virus replication (By similarity).<ref>PMID:9710605</ref> <ref>PMID:16530520</ref> <ref>PMID:17188392</ref>
	<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: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Piepenbrink~~, K H~~]]	+	[[Category: Piepenbrink KH]]
-	[[Category: Sundberg~~, E J]]~~	+	[[Category: Sundberg EJ]]
-	~~[[Category: Antibody]]~~	+
-	~~[[Category: Antigen]]~~	+
-	~~[[Category: Hcv]]~~	+
-	~~[[Category: Vaccine]]~~	+
-	~~[[Category: Viral protein-immune system complex]]~~	+
-	~~[[Category: Virology~~]]	+

OCA at 06:38, 5 August 2020

OCA — Wed, 05 Aug 2020 06:38:04 GMT

←Older revision		Revision as of 06:38, 5 August 2020
Line 1:		Line 1:

	==Structure of the HCV1-C1 Antibody-Antigen Complex==		==Structure of the HCV1-C1 Antibody-Antigen Complex==
-	<StructureSection load='5kzp' size='340' side='right' caption='[[5kzp]], [[Resolution\|resolution]] 2.26Å' scene=''>	+	<StructureSection load='5kzp' size='340' side='right'caption='[[5kzp]], [[Resolution\|resolution]] 2.26Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5kzp]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KZP OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5KZP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5kzp]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KZP OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5KZP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=5kzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kzp OCA], [http://pdbe.org/5kzp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kzp RCSB], [http://www.ebi.ac.uk/pdbsum/5kzp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kzp ProSAT]</span></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=5kzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kzp OCA], [http://pdbe.org/5kzp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kzp RCSB], [http://www.ebi.ac.uk/pdbsum/5kzp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kzp 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 5kzp" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5kzp" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Antibody 3D structures\|Antibody 3D structures]]
		+	*[[3D structures of human antibody\|3D structures of human antibody]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Piepenbrink, K H]]		[[Category: Piepenbrink, K H]]
	[[Category: Sundberg, E J]]		[[Category: Sundberg, E J]]

OCA at 11:06, 24 August 2017

OCA — Thu, 24 Aug 2017 11:06:39 GMT

←Older revision		Revision as of 11:06, 24 August 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5kzp is ~~ON HOLD until Paper~~ Publication	+	==Structure of the HCV1-C1 Antibody-Antigen Complex==
		+	<StructureSection load='5kzp' size='340' side='right' caption='[[5kzp]], [[Resolution\|resolution]] 2.26Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5kzp]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KZP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KZP FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=5kzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kzp OCA], [http://pdbe.org/5kzp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kzp RCSB], [http://www.ebi.ac.uk/pdbsum/5kzp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kzp ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response, thus an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412-423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope. This resulted in epitope-based immunogens based on a cyclic defensin protein, as well as a bivalent immunogen with two copies of the epitope on the E2 surface. We solved the x-ray structure of a cyclic immunogen in complex with the HCV1 antibody and confirmed preservation of the epitope conformation and the HCV1 interface. Mice vaccinated with our designed immunogens produced robust antibody responses to epitope I, and their serum could neutralize HCV. Notably, the cyclic designs induced greater epitope-specific responses and neutralization than the native peptide epitope. Beyond successfully designing several novel HCV immunogens, this study demonstrates the principle that neutralizing anti-HCV antibodies can be induced by epitope-based, engineered vaccines and provides the basis for further efforts in structure-based design of HCV vaccines.IMPORTANCE Hepatitis C virus is a leading cause of liver disease and liver cancer, with approximately 3% of the world's population infected. To combat this virus, an effective vaccine would have distinct advantages over current therapeutic options, yet experimental vaccines have not been successful to date, due in part to the virus's high sequence variability leading to immune escape. In this study we rationally designed several vaccine immunogens based on the structure of a conserved epitope that is the target of broadly neutralizing antibodies. In vivo results in mice indicated that these antigens elicited epitope-specific neutralizing antibodies, with varying degrees of potency and breadth. These promising results suggest that a rational design approach can be used to generate an effective vaccine for this virus.

-	~~Authors:~~ Piepenbrink, ~~K.H.~~, Sundberg, E.J.	+	Structure-Based Design of Hepatitis C Virus Vaccines that Elicit Neutralizing Antibody Responses to a Conserved Epitope.,Pierce BG, Boucher EN, Piepenbrink KH, Ejemel M, Rapp CA, Thomas WD Jr, Sundberg EJ, Weng Z, Wang Y J Virol. 2017 Aug 9. pii: JVI.01032-17. doi: 10.1128/JVI.01032-17. PMID:28794021<ref>PMID:28794021</ref>

-	~~Description: Structure~~ of the ~~HCV1~~-~~C1 Antibody~~-~~Antigen Complex~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: Piepenbrink, K.H]]	+	<div class="pdbe-citations 5kzp" style="background-color:#fffaf0;"></div>
-	[[Category: Sundberg, E.J]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Piepenbrink, K H]]
		+	[[Category: Sundberg, E J]]
		+	[[Category: Antibody]]
		+	[[Category: Antigen]]
		+	[[Category: Hcv]]
		+	[[Category: Vaccine]]
		+	[[Category: Viral protein-immune system complex]]
		+	[[Category: Virology]]

OCA at 14:28, 9 September 2016

OCA — Fri, 09 Sep 2016 14:28:40 GMT

←Older revision		Revision as of 14:28, 9 September 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5kzp is ON HOLD	+	The entry 5kzp is ON HOLD until Paper Publication

	Authors: Piepenbrink, K.H., Sundberg, E.J.		Authors: Piepenbrink, K.H., Sundberg, E.J.

-	Description: Structure of the HCV1-C3 Antibody-Antigen Complex	+	Description: Structure of the HCV1-C1 Antibody-Antigen Complex
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Piepenbrink, K.H]]		[[Category: Piepenbrink, K.H]]
	[[Category: Sundberg, E.J]]		[[Category: Sundberg, E.J]]

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

OCA — Thu, 04 Aug 2016 02:17:22 GMT

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

←Older revision

Revision as of 02:17, 4 August 2016

OCA: New page: '''Unreleased structure''' The entry 5kzp is ON HOLD Authors: Piepenbrink, K.H., Sundberg, E.J. Description: Structure of the HCV1-C3 Antibody-Antigen Complex [[Category: Unreleased St...

OCA — Thu, 04 Aug 2016 02:17:20 GMT

New page: '''Unreleased structure''' The entry 5kzp is ON HOLD Authors: Piepenbrink, K.H., Sundberg, E.J. Description: Structure of the HCV1-C3 Antibody-Antigen Complex [[Category: Unreleased St...

New page

'''Unreleased structure'''

The entry 5kzp is ON HOLD

Authors: Piepenbrink, K.H., Sundberg, E.J.

Description: Structure of the HCV1-C3 Antibody-Antigen Complex
[[Category: Unreleased Structures]]
[[Category: Piepenbrink, K.H]]
[[Category: Sundberg, E.J]]