OCA at 15:58, 18 October 2023

2023-10-18T15:58:25Z

←Older revision		Revision as of 15:58, 18 October 2023
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-	====	+	==Crystal structure of the human neutralizing antibody Fab fragment T025 bound to TBEV EDIII (Siberian Subtype)==
-	<StructureSection load='7lsg' size='340' side='right'caption='[[7lsg]]' scene=''>	+	<StructureSection load='7lsg' size='340' side='right'caption='[[7lsg]], [[Resolution\|resolution]] 1.86Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7lsg]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Tick-borne_encephalitis_virus Tick-borne encephalitis virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LSG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LSG 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=7lsg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lsg OCA], [https://pdbe.org/7lsg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lsg RCSB], [https://www.ebi.ac.uk/pdbsum/7lsg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lsg 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]] 1.86Å</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=7lsg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lsg OCA], [https://pdbe.org/7lsg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lsg RCSB], [https://www.ebi.ac.uk/pdbsum/7lsg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lsg ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/POLG_TBEVW POLG_TBEVW] Capsid protein C self-assembles to form an icosahedral capsid about 30 nm in diameter. The capsid encapsulates the genomic RNA (By similarity). prM acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is matured in the last step of virion assembly, presumably to avoid catastrophic activation of the viral fusion peptide induced by the acidic pH of the trans-Golgi network. After cleavage by host furin, the pr peptide is released in the extracellular medium and small envelope protein M and envelope protein E homodimers are dissociated (By similarity). Envelope protein E binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes (By similarity). Non-structural protein 1 is involved in virus replication and regulation of the innate immune response (By similarity). Non-structural protein 2A may be involved viral RNA replication and capsid assembly (Potential). Non-structural protein 2B is a required cofactor for the serine protease function of NS3 (By similarity). Serine protease NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS2B, performs its autocleavage and cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and unwinds dsRNA in the 3' to 5' direction (By similarity). Non-structural protein 4A induces host endoplasmic reticulum membrane rearrangements leading to the formation of virus-induced membranous vesicles hosting the dsRNA and polymerase, functioning as a replication complex. NS4A might also regulate the ATPase activity of the NS3 helicase (By similarity). Peptide 2k functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter (By similarity). RNA-directed RNA polymerase NS5 replicates the viral (+) and (-) genome, and performs the capping of genomes in the cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions. Besides its role in genome replication, also prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Inhibits host SCRIB and prevents activation of downstream JAK-STAT signaling pathway (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Tick-borne encephalitis virus (TBEV) is an emerging human pathogen that causes potentially fatal disease with no specific treatment. Mouse monoclonal antibodies are protective against TBEV, but little is known about the human antibody response to infection. Here, we report on the human neutralizing antibody response to TBEV in a cohort of infected and vaccinated individuals. Expanded clones of memory B cells expressed closely related anti-envelope domain III (EDIII) antibodies in both groups of volunteers. However, the most potent neutralizing antibodies, with IC50s below 1 ng/ml, were found only in individuals who recovered from natural infection. These antibodies also neutralized other tick-borne flaviviruses, including Langat, louping ill, Omsk hemorrhagic fever, Kyasanur forest disease, and Powassan viruses. Structural analysis revealed a conserved epitope near the lateral ridge of EDIII adjoining the EDI-EDIII hinge region. Prophylactic or early therapeutic antibody administration was effective at low doses in mice that were lethally infected with TBEV.
		+
		+	Broad and potent neutralizing human antibodies to tick-borne flaviviruses protect mice from disease.,Agudelo M, Palus M, Keeffe JR, Bianchini F, Svoboda P, Salat J, Peace A, Gazumyan A, Cipolla M, Kapoor T, Guidetti F, Yao KH, Elsterova J, Teislerova D, Chrdle A, Honig V, Oliveira T, West AP, Lee YE, Rice CM, MacDonald MR, Bjorkman PJ, Ruzek D, Robbiani DF, Nussenzweig MC J Exp Med. 2021 May 3;218(5):e20210236. doi: 10.1084/jem.20210236. PMID:33831141<ref>PMID:33831141</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7lsg" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Antibody 3D structures\|Antibody 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Z-~~disk~~]]	+	[[Category: Tick-borne encephalitis virus]]
		+	[[Category: Bjorkman PJ]]
		+	[[Category: Keeffe JR]]

OCA at 06:53, 7 April 2021

2021-04-07T06:53:47Z

←Older revision		Revision as of 06:53, 7 April 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7lsg ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7lsg' size='340' side='right'caption='[[7lsg]]' scene=''>
-	~~Authors~~: ~~Keeffe, J~~.R.~~, Bjorkman, P~~.J.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description: Crystal structure of~~ the ~~human neutralizing antibody Fab fragment T025 bound to TBEV EDIII (Siberian Subtype)~~	+	</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=7lsg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lsg OCA], [https://pdbe.org/7lsg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lsg RCSB], [https://www.ebi.ac.uk/pdbsum/7lsg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lsg ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Keeffe~~, J.R]]	+	__TOC__
-	[[Category: ~~Bjorkman, P.J~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 05:23, 17 March 2021

2021-03-17T05:23:33Z

←Older revision		Revision as of 05:23, 17 March 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7lsg is ON HOLD	+	The entry 7lsg is ON HOLD until Paper Publication

	Authors: Keeffe, J.R., Bjorkman, P.J.		Authors: Keeffe, J.R., Bjorkman, P.J.

OCA: Protected "7lsg" [edit=sysop:move=sysop]

2021-02-24T05:43:38Z

Protected "7lsg" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:43, 24 February 2021

OCA: New page: '''Unreleased structure''' The entry 7lsg is ON HOLD Authors: Keeffe, J.R., Bjorkman, P.J. Description: Crystal structure of the human neutralizing antibody Fab fragment T025 bound to ...

2021-02-24T05:43:37Z

New page: '''Unreleased structure''' The entry 7lsg is ON HOLD Authors: Keeffe, J.R., Bjorkman, P.J. Description: Crystal structure of the human neutralizing antibody Fab fragment T025 bound to ...

New page

'''Unreleased structure'''

The entry 7lsg is ON HOLD

Authors: Keeffe, J.R., Bjorkman, P.J.

Description: Crystal structure of the human neutralizing antibody Fab fragment T025 bound to TBEV EDIII (Siberian Subtype)
[[Category: Unreleased Structures]]
[[Category: Keeffe, J.R]]
[[Category: Bjorkman, P.J]]

7lsg - Revision history

OCA at 15:58, 18 October 2023

OCA at 06:53, 7 April 2021

OCA at 05:23, 17 March 2021

OCA: Protected "7lsg" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7lsg is ON HOLD Authors: Keeffe, J.R., Bjorkman, P.J. Description: Crystal structure of the human neutralizing antibody Fab fragment T025 bound to ...