6xw4 - Revision history

OCA at 13:13, 24 January 2024

OCA — Wed, 24 Jan 2024 13:13:59 GMT

←Older revision		Revision as of 13:13, 24 January 2024
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	<StructureSection load='6xw4' size='340' side='right'caption='[[6xw4]], [[Resolution\|resolution]] 2.19Å' scene=''>		<StructureSection load='6xw4' size='340' side='right'caption='[[6xw4]], [[Resolution\|resolution]] 2.19Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6xw4]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Alpaca Alpaca~~] and [~~http~~://en.wikipedia.org/wiki/~~Murine_norovirus_1 Murine norovirus 1~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XW4 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6XW4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6xw4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Murine_norovirus_1 Murine norovirus 1] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XW4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XW4 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 2.19Å</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=6xw4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xw4 OCA], [~~http~~://pdbe.org/6xw4 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6xw4 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6xw4 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6xw4 ProSAT]</span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=6xw4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xw4 OCA], [https://pdbe.org/6xw4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xw4 RCSB], [https://www.ebi.ac.uk/pdbsum/6xw4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xw4 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/Q80J94_9CALI Q80J94_9CALI]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 6xw4" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6xw4" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Antibody 3D structures\|Antibody 3D structures]]
		+	*[[Virus coat proteins 3D structures\|Virus coat proteins 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Alpaca]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Murine norovirus 1]]		[[Category: Murine norovirus 1]]
-	[[Category: ~~Hansman, G~~]]	+	[[Category: Vicugna pacos]]
-	[[Category: ~~Kilic, T~~]]	+	[[Category: Hansman G]]
-	[[Category: ~~Sabin, C~~]]	+	[[Category: Kilic T]]
-	[[Category: ~~Mnv]]~~	+	[[Category: Sabin C]]
-	~~[[Category: Neutralizing nanobody]]~~	+
-	~~[[Category: Norovirus]]~~	+
-	~~[[Category: Vhh]]~~	+
-	~~[[Category: Viral protein~~]]	+

OCA at 06:46, 6 May 2020

OCA — Wed, 06 May 2020 06:46:15 GMT

←Older revision		Revision as of 06:46, 6 May 2020
Line 1:		Line 1:

	==Crystal structure of murine norovirus P domain in complex with Nanobody NB-5867==		==Crystal structure of murine norovirus P domain in complex with Nanobody NB-5867==
-	<StructureSection load='6xw4' size='340' side='right'caption='[[6xw4]]' scene=''>	+	<StructureSection load='6xw4' size='340' side='right'caption='[[6xw4]], [[Resolution\|resolution]] 2.19Å' 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=6XW4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6XW4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6xw4]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Alpaca Alpaca] and [http://en.wikipedia.org/wiki/Murine_norovirus_1 Murine norovirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XW4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6XW4 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=6xw4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xw4 OCA], [http://pdbe.org/6xw4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6xw4 RCSB], [http://www.ebi.ac.uk/pdbsum/6xw4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6xw4 ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=6xw4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xw4 OCA], [http://pdbe.org/6xw4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6xw4 RCSB], [http://www.ebi.ac.uk/pdbsum/6xw4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6xw4 ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Human norovirus frequently causes outbreaks of acute gastroenteritis. Although discovered more than five decades ago, antiviral development has, until recently, been hampered by the lack of a reliable human norovirus cell culture system. Nevertheless, a lot of pathogenesis studies were accomplished using murine norovirus (MNV), which can be grown routinely in cell culture. In this study, we analysed a sizeable library of Nanobodies that were raised against the murine norovirus virion with the main purpose of developing Nanobody-based inhibitors. We discovered two types of neutralizing Nanobodies and analysed the inhibition mechanisms using X-ray crystallography, cryo-EM, and cell culture techniques. The first type bound on the top region of the protruding (P) domain. Interestingly, the Nanobody binding region closely overlapped the MNV receptor-binding site and collectively shared numerous P domain-binding residues. In addition, we showed that these Nanobodies competed with the soluble receptor and this action blocked virion attachment to cultured cells. The second type bound at a dimeric interface on the lower side of the P dimer. We discovered that these Nanobodies disrupted a structural change in the capsid associated with binding co-factors (i.e., metal cations/bile acid). Indeed, we found that capsids underwent major conformational changes following addition of Mg(2+) or Ca(2+) Ultimately, these Nanobodies directly obstructed a structural modification reserved for a post-receptor attachment stage. Altogether, our new data show that Nanobody-based inhibition could occur by blocking functional and structural capsid properties.IMPORTANCE This research discovered and analysed two different types of MNV neutralizing Nanobodies. The top-binding Nanobodies sterically inhibited the receptor-binding site, whereas the dimeric-binding Nanobodies interfered with a structural modification associated with co-factor binding. Moreover, we found that the capsid contained a number of vulnerable regions that were essential for viral replication. In fact, the capsid appeared to be organized in a state of flux, which could be important for co-factor/receptor binding functions. Blocking these capsid-binding events with Nanobodies directly inhibited essential capsid functions. Moreover, a number of MNV-specific Nanobody binding epitopes were comparable to human norovirus-specific Nanobody inhibitors. Therefore, this additional structural and inhibition information could be further exploited in the development of human norovirus antivirals.
		+
		+	Nanobody mediated neutralization reveals an Achilles heel for norovirus.,Koromyslova AD, Devant JM, Kilic T, Sabin CD, Malak V, Hansman GS J Virol. 2020 Apr 22. pii: JVI.00660-20. doi: 10.1128/JVI.00660-20. PMID:32321816<ref>PMID:32321816</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6xw4" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Alpaca]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Hansman G]]	+	[[Category: Murine norovirus 1]]
-	[[Category: Kilic T]]	+	[[Category: Hansman, G]]
-	[[Category: Sabin C]]	+	[[Category: Kilic, T]]
		+	[[Category: Sabin, C]]
		+	[[Category: Mnv]]
		+	[[Category: Neutralizing nanobody]]
		+	[[Category: Norovirus]]
		+	[[Category: Vhh]]
		+	[[Category: Viral protein]]

OCA at 05:49, 22 April 2020

OCA — Wed, 22 Apr 2020 05:49:43 GMT

←Older revision		Revision as of 05:49, 22 April 2020
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-	'''Unreleased structure'''

-	~~The entry 6xw4 is ON HOLD until Paper Publication~~	+	==Crystal structure of murine norovirus P domain in complex with Nanobody NB-5867==
-		+	<StructureSection load='6xw4' size='340' side='right'caption='[[6xw4]]' scene=''>
-	~~Authors: Kilic, T., Sabin, C., Hansman, G.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XW4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6XW4 FirstGlance]. <br>
-	~~Description:~~ Crystal structure of murine norovirus P domain in complex with Nanobody NB-5867	+	</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=6xw4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xw4 OCA], [http://pdbe.org/6xw4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6xw4 RCSB], [http://www.ebi.ac.uk/pdbsum/6xw4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6xw4 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Sabin, C~~]]	+	__TOC__
-	[[Category: Kilic, T]]	+	</StructureSection>
-	[[Category: ~~Hansman, G~~]]	+	[[Category: Large Structures]]
		+	[[Category: Hansman G]]
		+	[[Category: Kilic T]]
		+	[[Category: Sabin C]]

OCA at 08:30, 27 March 2020

OCA — Fri, 27 Mar 2020 08:30:50 GMT

←Older revision		Revision as of 08:30, 27 March 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6xw4 is ON HOLD	+	The entry 6xw4 is ON HOLD until Paper Publication

	Authors: Kilic, T., Sabin, C., Hansman, G.		Authors: Kilic, T., Sabin, C., Hansman, G.
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	Description: Crystal structure of murine norovirus P domain in complex with Nanobody NB-5867		Description: Crystal structure of murine norovirus P domain in complex with Nanobody NB-5867
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
		+	[[Category: Sabin, C]]
	[[Category: Kilic, T]]		[[Category: Kilic, T]]
	[[Category: Hansman, G]]		[[Category: Hansman, G]]
-	[[Category: Sabin, C]]

OCA: Protected "6xw4" [edit=sysop:move=sysop]

OCA — Wed, 29 Jan 2020 13:51:07 GMT

Protected "6xw4" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:51, 29 January 2020

OCA: New page: '''Unreleased structure''' The entry 6xw4 is ON HOLD Authors: Kilic, T., Sabin, C., Hansman, G. Description: Crystal structure of murine norovirus P domain in complex with Nanobody NB-...

OCA — Wed, 29 Jan 2020 13:51:05 GMT

New page: '''Unreleased structure''' The entry 6xw4 is ON HOLD Authors: Kilic, T., Sabin, C., Hansman, G. Description: Crystal structure of murine norovirus P domain in complex with Nanobody NB-...

New page

'''Unreleased structure'''

The entry 6xw4 is ON HOLD

Authors: Kilic, T., Sabin, C., Hansman, G.

Description: Crystal structure of murine norovirus P domain in complex with Nanobody NB-5867
[[Category: Unreleased Structures]]
[[Category: Kilic, T]]
[[Category: Hansman, G]]
[[Category: Sabin, C]]