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| | <StructureSection load='5sv3' size='340' side='right'caption='[[5sv3]], [[Resolution|resolution]] 2.73Å' scene=''> | | <StructureSection load='5sv3' size='340' side='right'caption='[[5sv3]], [[Resolution|resolution]] 2.73Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5sv3]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Camelus_glama Camelus glama] and [http://en.wikipedia.org/wiki/Castor_bean Castor bean]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SV3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5SV3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5sv3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Lama_glama Lama glama] and [https://en.wikipedia.org/wiki/Ricinus_communis Ricinus communis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SV3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SV3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.73Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5sv4|5sv4]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/rRNA_N-glycosylase rRNA N-glycosylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.22 3.2.2.22] </span></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=5sv3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sv3 OCA], [https://pdbe.org/5sv3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5sv3 RCSB], [https://www.ebi.ac.uk/pdbsum/5sv3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5sv3 ProSAT]</span></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=5sv3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5sv3 OCA], [http://pdbe.org/5sv3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5sv3 RCSB], [http://www.ebi.ac.uk/pdbsum/5sv3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5sv3 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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). | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| | *[[Antibody 3D structures|Antibody 3D structures]] | | *[[Antibody 3D structures|Antibody 3D structures]] |
| - | *[[Ricin|Ricin]] | + | *[[Ricin 3D structures|Ricin 3D structures]] |
| | + | *[[3D structures of non-human antibody|3D structures of non-human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Camelus glama]] | + | [[Category: Lama glama]] |
| - | [[Category: Castor bean]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: RRNA N-glycosylase]] | + | [[Category: Ricinus communis]] |
| - | [[Category: Compton, J R]] | + | [[Category: Compton JR]] |
| - | [[Category: Legler, P M]] | + | [[Category: Legler PM]] |
| - | [[Category: A-chain]]
| + | |
| - | [[Category: Antibody]]
| + | |
| - | [[Category: Ricin]]
| + | |
| - | [[Category: Rta1-33/44-198]]
| + | |
| - | [[Category: Rvec]]
| + | |
| - | [[Category: Sdab]]
| + | |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
Function
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).
Publication Abstract from PubMed
Ricin is an A-B ribosome inactivating protein (RIP) toxin composed of an A-chain subunit (RTA) that contains a catalytic N-glycosidase and a B-chain (RTB) lectin domain that binds cell surface glycans. Ricin exploits retrograde transport to enter into the Golgi and the endoplasmic reticulum, and then dislocates into the cytoplasm where it can reach its substrate, the ribosomal RNA. A subset of isolated antibodies (Abs) raised against the RTA subunit protect against ricin intoxication, and RTA-based vaccine immunogens have been shown to provide long-lasting protective immunity against the holotoxin. Anti-RTA Abs are unlikely to cross a membrane and reach the cytoplasm to inhibit the enzymatic activity of the A-chain. Moreover, there is not a strict correlation between the apparent binding affinity (Ka) of anti-RTA Abs and their ability to successfully neutralize ricin toxicity. Some anti-RTA antibodies are toxin-neutralizing, whereas others are not. We hypothesize that neutralizing anti-RTA Abs may interfere selectively with conformational change(s) or partial unfolding required for toxin internalization. To test this hypothesis, we measured the melting temperatures (Tm) of neutralizing single-domain Ab (sdAb)-antigen (Ag) complexes relative to the Tm of the free antigen (Tm-shift = Tmcomplex - TmAg), and observed increases in the Tmcomplex of 9-20 degrees. In contrast, non-neutralizing sdAb-Ag complexes shifted the TmComplex by only 6-7 degrees. A strong linear correlation (r2 = 0.992) was observed between the magnitude of the Tm-shift and the viability of living cells treated with the sdAb and ricin holotoxin. The Tm-shift of the sdAb-Ag complex provided a quantitative biophysical parameter that could be used to predict and rank-order the toxin-neutralizing activities of Abs. We determined the first structure of an sdAb-RTA1-33/44-198 complex, and examined other sdAb-RTA complexes. We found that neutralizing sdAb bound to regions involved in the early stages of unfolding. These Abs likely interfere with steps preceding or following endocytosis that require conformational changes. This method may have utility for the characterization or rapid screening of other Ab that act to prevent conformational changes or unfolding as part of their mechanism of action.
Stability of isolated antibody-antigen complexes as a predictive tool for selecting toxin neutralizing antibodies.,Legler PM, Compton JR, Hale ML, Anderson GP, Olson MA, Millard CB, Goldman ER MAbs. 2016 Sep 23:0. PMID:27660893[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Legler PM, Compton JR, Hale ML, Anderson GP, Olson MA, Millard CB, Goldman ER. Stability of isolated antibody-antigen complexes as a predictive tool for selecting toxin neutralizing antibodies. MAbs. 2016 Sep 23:0. PMID:27660893 doi:http://dx.doi.org/10.1080/19420862.2016.1236882
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