View source for 7kdu


==Ricin bound to VHH antibody V5E4==
<StructureSection load='7kdu' size='340' side='right'caption='[[7kdu]], [[Resolution|resolution]] 2.81&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7kdu]] is a 3 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=7KDU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KDU 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]] 2.809&#8491;</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>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7kdu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kdu OCA], [https://pdbe.org/7kdu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kdu RCSB], [https://www.ebi.ac.uk/pdbsum/7kdu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kdu ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Ricin toxin kills mammalian cells with notorious efficiency. The toxin's B subunit (RTB) is a Gal/GalNAc-specific lectin that attaches to cell surfaces and promotes retrograde transport of ricin's A subunit (RTA) to the trans Golgi network (TGN) and endoplasmic reticulum (ER). RTA is liberated from RTB in the ER and translocated into the cell cytoplasm, where it functions as a ribosome-inactivating protein. While antibodies against ricin's individual subunits have been reported, we now describe seven alpaca-derived, single-domain antibodies (V(H)Hs) that span the RTA-RTB interface, including four Tier 1 V(H)Hs with IC(50) values &lt;1 nM. Crystal structures of each V(H)H bound to native ricin holotoxin revealed three different binding modes, based on contact with RTA's F-G loop (mode 1), RTB's subdomain 2gamma (mode 2) or both (mode 3). V(H)Hs in modes 2 and 3 were highly effective at blocking ricin attachment to HeLa cells and immobilized asialofetuin, due to framework residues (FR3) that occupied the 2gamma Gal/GalNAc-binding pocket and mimic ligand. The four Tier 1 V(H)Hs also interfered with intracellular functions of RTB, as they neutralized ricin in a post-attachment cytotoxicity assay (e.g., the toxin was bound to cell surfaces before antibody addition) and reduced the efficiency of toxin transport to the TGN. We conclude that the RTA-RTB interface is a target of potent toxin-neutralizing antibodies that interfere with both extracellular and intracellular events in ricin's cytotoxic pathway.

Structural Analysis of Toxin-Neutralizing, Single-Domain Antibodies that Bridge Ricin's A-B Subunit Interface.,Rudolph MJ, Poon AY, Kavaliauskiene S, Myrann AG, Reynolds-Peterson C, Davis SA, Sandvig K, Vance DJ, Mantis NJ J Mol Biol. 2021 Jul 23;433(15):167086. doi: 10.1016/j.jmb.2021.167086. Epub 2021 , Jun 3. PMID:34089718<ref>PMID:34089718</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7kdu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Ricin 3D structures|Ricin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Ricinus communis]]
[[Category: Vicugna pacos]]
[[Category: Rudolph MJ]]