Ricin: Difference between revisions

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<StructureSection load='3rtj'  size='400' side='right' caption='Glycosylated ricin chain A (grey) and chain B (green) bound to dinucleotide APG (stick model) (PDB entry [[3rtj]])'>
<StructureSection load='3rtj'  size='400' side='right' caption='Glycosylated ricin chain A (grey) and chain B (green) bound to dinucleotide APG (stick model) (PDB entry [[3rtj]])'>
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==Structure==
==Structure==
Ricin is a heterodimer that consists of a 32 kilodalton A chain glycoprotein (light blue) linked by a <scene name='38/382952/Disulfide_bond_between_subunit/3'>disulfide bond</scene> to a 32 kilodalton <scene name='Sandbox_BCMB402_Ricin/B_subunit/1'>B chain</scene> glycoprotein<ref name="montfort" /> (green).  
Ricin is a heterodimer that consists of a 32 kilodalton A chain glycoprotein (light blue) linked by a <scene name='38/382952/Disulfide_bond_between_subunit/3'>disulfide bond</scene> to a 32 kilodalton <scene name='Sandbox_BCMB402_Ricin/B_subunit/1'>B chain</scene> glycoprotein<ref name="montfort" /> (green).  
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The B chain is a lectin<ref name="lord" /> that <scene name='Sandbox_BCMB402_Ricin/Carbohydrate_binding/1'>binds</scene> to galactose-containing surface receptors.  Originally it was thought that the mode of action of Ricin poisoning was due to hemagglutination due to a closely related, co-isolating lectin, RCA.  
The B chain is a lectin<ref name="lord" /> that <scene name='Sandbox_BCMB402_Ricin/Carbohydrate_binding/1'>binds</scene> to galactose-containing surface receptors.  Originally it was thought that the mode of action of Ricin poisoning was due to hemagglutination due to a closely related, co-isolating lectin, RCA.  


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==Mechanism of action==
==Mechanism of action==
The mechanism deployed by Ricin to gain entry to a host cell involves the poison's heterogenic properties. First, the B subunit binds to two carbohydrates on the cell surface, either glycolipids or glycoproteins, which both terminate with galactose.  The interaction is facilitated by hydrogen bonds to <scene name='Sandbox_BCMB402_Ricin/B_chain_bind_lactose_1/2'>lysine 40 and asparagine 46</scene> in one domain<ref name = "Rutenber">PMID: 3561502</ref> and <scene name='Sandbox_BCMB402_Ricin/B_chain_bind_lactose_2/1'>asparagine 255</scene> in the other domain. Once bound, the ricin-glycoprotein complex is taken into the cells via endocytosis.  This association between the A and B chain is essential for toxicity <ref name="montfort" /> without it the Ricin would not be able to gain access to the cell, rendering it useless<ref name = "rapak">PMID: 9108055</ref>.  The endocytotic pathway results in the cleavage of the disulfide bond linking the A and B chains.  After cleavage, the A chain is released into the cytosol.
The mechanism deployed by Ricin to gain entry to a host cell involves the poison's heterogenic properties. First, the B subunit binds to two carbohydrates on the cell surface, either glycolipids or glycoproteins, which both terminate with galactose.  The interaction is facilitated by hydrogen bonds to <scene name='Sandbox_BCMB402_Ricin/B_chain_bind_lactose_1/2'>lysine 40 and asparagine 46</scene> in one domain<ref name = "Rutenber">PMID: 3561502</ref> and <scene name='Sandbox_BCMB402_Ricin/B_chain_bind_lactose_2/1'>asparagine 255</scene> in the other domain. Once bound, the ricin-glycoprotein complex is taken into the cells via endocytosis.  This association between the A and B chain is essential for toxicity <ref name="montfort" /> without it the Ricin would not be able to gain access to the cell, rendering it useless<ref name = "rapak">PMID: 9108055</ref>.  The endocytotic pathway results in the cleavage of the disulfide bond linking the A and B chains.  After cleavage, the A chain is released into the cytosol.
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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===Ricin A chain (RTA)===
===Ricin A chain (RTA)===


[[1j1m]], [[1ift]], [[2aai]], [[1rtc]] – RTA<br />
[[1j1m]], [[1ift]], [[2aai]], [[1rtc]] – RTA<br />
[[3lc9]], [[3mk9]], [[2vc4]], [[1uq4]], [[1uq5]], [[1obs]], [[3bjg]], [[3srp]], [[4imv]] – RTA (mutant)
[[3lc9]], [[3mk9]], [[2vc4]], [[1uq4]], [[1uq5]], [[1obs]], [[3bjg]], [[3srp]], [[4imv]] – RTA (mutant)
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===Ricin A chain binary complexes===
''Ricin A chain binary complexes''


[[3px8]] – RTA preproricin + 7-carboxy-pterin<br />
[[3px8]] – RTA preproricin + 7-carboxy-pterin<br />
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[[3px8]] – RTA + formycin monophosphate<br />
[[3px8]] – RTA + formycin monophosphate<br />
[[4kuc]] – RTA + antibody<br />
[[4kuc]] – RTA + antibody<br />
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===Ricin B chain (RTB)===
===Ricin B chain (RTB)===


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[[3vt1]], [[3vt2]] – CtRTB lectin domain + galactose derivative<br />
[[3vt1]], [[3vt2]] – CtRTB lectin domain + galactose derivative<br />


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===Ricin A+B chains===
===Ricin A+B chains===


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[[3rtj]] - RTA + RTB + dinucleotide
[[3rtj]] - RTA + RTB + dinucleotide


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==See Also==
==See Also==
* [[Ribosome]]
* [[Ribosome]]
* [[Large Ribosomal Subunit of Haloarcula|Large Ribosomal Subunit]]
* [[Large Ribosomal Subunit of Haloarcula|Large Ribosomal Subunit]]
* [[Translation]]
* [[Translation]]
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==References==
==References==
{{Reflist}}
{{Reflist}}


[[Category: Topic Page]]
[[Category: Topic Page]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Andrea Gorrell, Douglas Read, David Canner, Michal Harel, Wayne Decatur, Alexander Berchansky, Ann Taylor, Jaime Prilusky, Joel L. Sussman, Angel Herraez