OCA at 17:04, 18 October 2023

OCA — Wed, 18 Oct 2023 17:04:24 GMT

←Older revision		Revision as of 17:04, 18 October 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 7th2 is ~~ON HOLD until Paper~~ Publication	+	==Single-domain VHH intrabodies neutralize ricin toxin==
		+	<StructureSection load='7th2' size='340' side='right'caption='[[7th2]], [[Resolution\|resolution]] 1.84Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7th2]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Ricinus_communis Ricinus communis] 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=7TH2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TH2 FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.838Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7th2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7th2 OCA], [https://pdbe.org/7th2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7th2 RCSB], [https://www.ebi.ac.uk/pdbsum/7th2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7th2 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/RICI_RICCO RICI_RICCO] Ricin is highly toxic to animal cells and to a lesser extent to plant cells. The A chain acts as a glycosidase that removes a specific adenine residue from an exposed loop of the 28S rRNA (A4324 in mammals), leading to rRNA breakage. As this loop is involved in elongation factor binding, modified ribosomes are catalytically inactive and unable to support protein synthesis. The A chain can inactivate a few thousand ribosomes per minute, faster than the cell can make new ones. Therefore a single A chain molecule can kill an animal cell. The B chain binds to beta-D-galactopyranoside moieties on cell surface glycoproteins and glycolipids and facilitates the entry into the cell of the A chain; B chains are also responsible for cell agglutination (Lectin activity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	During ricin intoxication in mammalian cells, ricin's enzymatic (RTA) and binding (RTB) subunits disassociate in the endoplasmic reticulum. RTA is then translocated into the cytoplasm where, by virtue of its ability to depurinate a conserved residue within the sarcin-ricin loop (SRL) of 28S rRNA, it functions as a ribosome-inactivating protein. It has been proposed that recruitment of RTA to the SRL is facilitated by ribosomal P-stalk proteins, whose C-terminal domains interact with a cavity on RTA normally masked by RTB; however, evidence that this interaction is critical for RTA activity within cells is lacking. Here, we characterized a collection of single-domain antibodies (V(H)Hs) whose epitopes overlap with the P-stalk binding pocket on RTA. The crystal structures of three such V(H)Hs (V9E1, V9F9, and V9B2) in complex with RTA revealed not only occlusion of the ribosomal P-stalk binding pocket but also structural mimicry of C-terminal domain peptides by complementarity-determining region 3. In vitro assays confirmed that these V(H)Hs block RTA-P-stalk peptide interactions and protect ribosomes from depurination. Moreover, when expressed as "intrabodies," these V(H)Hs rendered cells resistant to ricin intoxication. One V(H)H (V9F6), whose epitope was structurally determined to be immediately adjacent to the P-stalk binding pocket, was unable to neutralize ricin within cells or protect ribosomes from RTA in vitro. These findings are consistent with the recruitment of RTA to the SRL by ribosomal P-stalk proteins as a requisite event in ricin-induced ribosome inactivation.

-	~~Authors~~:	+	Single-domain antibodies neutralize ricin toxin intracellularly by blocking access to ribosomal P-stalk proteins.,Czajka TF, Vance DJ, Davis S, Rudolph MJ, Mantis NJ J Biol Chem. 2022 Apr;298(4):101742. doi: 10.1016/j.jbc.2022.101742. Epub 2022 , Feb 17. PMID:35182523<ref>PMID:35182523</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 7th2" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Ricinus communis]]
		+	[[Category: Vicugna pacos]]
		+	[[Category: Mantis N]]
		+	[[Category: Rudolph MJ]]

OCA at 06:29, 23 February 2022

OCA — Wed, 23 Feb 2022 06:29:02 GMT

←Older revision		Revision as of 06:29, 23 February 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7th2 is ON HOLD	+	The entry 7th2 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7th2" [edit=sysop:move=sysop]

OCA — Wed, 19 Jan 2022 06:01:55 GMT

Protected "7th2" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:01, 19 January 2022

OCA: New page: '''Unreleased structure''' The entry 7th2 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 19 Jan 2022 06:01:54 GMT

New page: '''Unreleased structure''' The entry 7th2 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7th2 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7th2 - Revision history

OCA at 17:04, 18 October 2023

OCA at 06:29, 23 February 2022

OCA: Protected "7th2" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7th2 is ON HOLD Authors: Description: Category: Unreleased Structures