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{{BAMBED
|DATE=May 14, 2013
|OLDID=1797961
|BAMBEDDOI=10.1002/bmb.20716
}}
'''Ricin''' is a potent cytotoxin that is synthesized in the endosperm cells of maturing seeds of the castor oil plant (''Ricinus communis'')<ref name="lord">PMID: 8119491</ref>. Ricin belongs to a small multi-gene family<ref name="montfort">PMID: 3558397</ref> that is composed of eight members. Ricin is classified as a type II heterodimeric Ribosome Inactivating Protein<ref name="lord" /> or RIPs.  For toxins in Proteopedia see [[Toxins]].
'''Ricin''' is a potent cytotoxin that is synthesized in the endosperm cells of maturing seeds of the castor oil plant (''Ricinus communis'')<ref name="lord">PMID: 8119491</ref>. Ricin belongs to a small multi-gene family<ref name="montfort">PMID: 3558397</ref> that is composed of eight members. Ricin is classified as a type II heterodimeric Ribosome Inactivating Protein<ref name="lord" /> or RIPs.  For toxins in Proteopedia see [[Toxins]].


<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]])'>
See also [[Ricin: A toxic protein]]; [[Ricin: Structure and function]].
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<StructureSection load='3rtj'  size='350' side='right' caption='Glycosylated ricin chain A (grey) and chain B (green) bound to dinucleotide APG (stick model) (PDB entry [[3rtj]])'>
==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/2'>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).  


The <scene name='Sandbox_BCMB402_Ricin/A_subunit_secondary_structure/2'> A chain</scene> is an alpha/beta protein which contains eight alpha helices (pink) and eight beta sheets (yellow). It has three domains<ref name="Weston">PMID: 7990130</ref>.  <scene name='Sandbox_BCMB402_Ricin/Domain_1_of_a_subunit/2'>Domain 1 </scene> consists of a beta sheet containing both parallel and anti-parallel strands.  The <scene name='Sandbox_BCMB402_Ricin/Domain2_of_a_subunit/1'> second alpha helical domain </scene> makes up the core of the protein, and includes the active site.  The<scene name='Sandbox_BCMB402_Ricin/Domain3_of_a_subunit/1'> third domain</scene> interacts with the B chain, and contains a helix and two beta strands.
The <scene name='Sandbox_BCMB402_Ricin/A_subunit_secondary_structure/2'> A chain</scene> is an alpha/beta protein which contains eight alpha helices (pink) and eight beta sheets (yellow). It has three domains<ref name="Weston">PMID: 7990130</ref>.  <scene name='Sandbox_BCMB402_Ricin/Domain_1_of_a_subunit/2'>Domain 1 </scene> consists of a beta sheet containing both parallel and anti-parallel strands.  The <scene name='Sandbox_BCMB402_Ricin/Domain2_of_a_subunit/1'> second alpha helical domain </scene> makes up the core of the protein, and includes the active site.  The<scene name='Sandbox_BCMB402_Ricin/Domain3_of_a_subunit/1'> third domain</scene> interacts with the B chain, and contains a helix and two beta strands.


The A chain contains the active site that is responsible for inactivating the [[Ribosome]] via depurination.  RIPs have very diverse structures, containing only eight invariant residues<ref name = "lord"/>.  These <scene name='Sandbox_BCMB402_Ricin/Conserved_residues/2'>conserved residues</scene> are clustered in the active site.
The '''A chain''' contains the active site that is responsible for inactivating the [[Ribosome]] via depurination.  RIPs have very diverse structures, containing only eight invariant residues<ref name = "lord"/>.  These <scene name='Sandbox_BCMB402_Ricin/Conserved_residues/2'>conserved residues</scene> are clustered in the active site.


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.  


__notoc__
==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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==3D structures of ricin==
==3D structures of ricin==
[[Ricin 3D structures]]


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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===Ricin A chain (RTA)===
[[1j1m]], [[1ift]], [[2aai]], [[1rtc]] – RTA<br />
[[3lc9]], [[3mk9]], [[2vc4]], [[1uq4]], [[1uq5]], [[1obs]], [[3bjg]], [[3srp]], [[4imv]] – RTA (mutant)
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===Ricin A chain binary complexes===
[[3px8]] – RTA preproricin + 7-carboxy-pterin<br />
[[1br5]], [[1br6]], [[4esi]], [[4huo]], [[4hup]], [[4hv3]], [[4hv7]], [[4mx1]], [[4mx5]] - RTA + pterin derivative<br />
[[3px9]] - RTA preproricin + furanylmethyl-carbamoyl-pterin<br />
[[3lc9]], [[3mk9]], [[2vc4]], [[1uq4]], [[1uq5]], [[1obs]] – RTA (mutant) <br />
[[3hio]] – RTA + tetranucleotide<br />
[[3ej5]], [[1il5]] – RTA pyrimidine derivative<br />
[[2p8n]], [[1ifs]] – RTA + adenine<br />
[[2pjo]], [[2r2x]] – RTA + urea derivative<br />
[[2r3d]] – RTA + acetamide<br />
[[2vc3]] - RTA (mutant) + acetate<br />
[[1il3]], [[1il4]], [[1il9]] – RTA + guanine derivative<br />
[[1ifu]], [[1fmp]] – RTA + formycin<br />
[[1obt]] - RTA (mutant) + AMP<br />
[[1apg]] – RTA + RNA
[[3px8]] – RTA + formycin monophosphate<br />
[[4kuc]] – RTA + antibody<br />
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===Ricin B chain (RTB)===
[[3nbc]], [[3nbd]] – CnRTB + lactose – ''Clitocybe nebularis''<br />
[[3nbe]] – CnRTB + lactose derivative<br />
[[3phz]] – RTB + glycoside – ''Polyporus squamosus''<br />
[[3vsf]] – CtRTB lectin domain – ''Clostridium thermocellum''<br />
[[3vsz]] – CtRTB lectin domain + galactan<br />
[[3vto]] – CtRTB lectin domain + lactose<br />
[[3vt1]], [[3vt2]] – CtRTB lectin domain + galactose derivative<br />
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===Ricin A+B chains===
[[2aai]] - RTA + RTB<br />
[[3px8]], [[3rti]] – RTA + RTB + formycin monophosphate<br />
[[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]]
[[Category:Featured in BAMBED]]

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
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