Ricin
From Proteopedia
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==3D structures of ricin== | ==3D structures of ricin== | ||
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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]] – RTA (mutant) | + | [[3lc9]], [[3mk9]], [[2vc4]], [[1uq4]], [[1uq5]], [[1obs]], [[3bjg]], [[3srp]] – RTA (mutant) |
===Ricin A chain binary complexes=== | ===Ricin A chain binary complexes=== | ||
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[[3lc9]], [[3mk9]], [[2vc4]], [[1uq4]], [[1uq5]], [[1obs]] – RTA (mutant) <br /> | [[3lc9]], [[3mk9]], [[2vc4]], [[1uq4]], [[1uq5]], [[1obs]] – RTA (mutant) <br /> | ||
[[3hio]] – RTA + tetranucleotide<br /> | [[3hio]] – RTA + tetranucleotide<br /> | ||
| - | [[3ej5]], [[ | + | [[3ej5]], [[1il5]] – RTA pyrimidine derivative<br /> |
[[2p8n]], [[1ifs]] – RTA + adenine<br /> | [[2p8n]], [[1ifs]] – RTA + adenine<br /> | ||
[[2pjo]], [[2r2x]] – RTA + urea derivative<br /> | [[2pjo]], [[2r2x]] – RTA + urea derivative<br /> | ||
[[2r3d]] – RTA + acetamide<br /> | [[2r3d]] – RTA + acetamide<br /> | ||
[[2vc3]] - RTA (mutant) + acetate<br /> | [[2vc3]] - RTA (mutant) + acetate<br /> | ||
| - | [[1il3]], [[ | + | [[1il3]], [[1il4]], [[1il9]] – RTA + guanine derivative<br /> |
[[1ifu]], [[1fmp]] – RTA + formycin<br /> | [[1ifu]], [[1fmp]] – RTA + formycin<br /> | ||
[[1obt]] - RTA (mutant) + AMP<br /> | [[1obt]] - RTA (mutant) + AMP<br /> | ||
[[1apg]] – RTA + RNA | [[1apg]] – RTA + RNA | ||
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| + | ===Ricin B chain (RTB)=== | ||
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| + | [[3nbc]], [[3nbd]] – CnRTB + lactose – ''Clitocybe nebularis''<br /> | ||
| + | [[3nbe]] – CnRTB + lactose derivative<br /> | ||
| + | [[3phz]] – RTB + glycoside – ''Polyporus squamosus'' | ||
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| + | ===Ricin A+B chains=== | ||
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| + | [[3px8]] – RTA + RTB + formycin monophosphate<br /> | ||
| + | [[3rjt]] - RTA + RTB + dinucleotide | ||
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==See Also== | ==See Also== | ||
Revision as of 09:57, 19 December 2011
Introduction
Ricin is a potent cytotoxin that is synthesized in the endosperm cells of maturing seeds of the castor oil plant (Ricinus communis)[1]. Ricin belongs to a small multi-gene family[2] that is composed of eight members. Ricin is classified as a type II heterodimeric Ribosome Inactivatiing protein[1].
Structure
is a heterodimer that consists of a 32 kilodalton A chain glycoprotein linked by a disulfide bond to a 32 kilodalton B chain glycoprotein[2]. The A chain enzyme is a globular protein with extensive secondary structure and a predominate active site[2]; where the B chain is a lectin[1] that binds to galactose-containing surface receptors[3].
Physiology
The mechanism deployed by Ricin to gain entry to a host cell involves the poison's heterogenic properties. First, the toxin arranges itself in such a way where its B chain can easily interact with the host cells receptors, and once acknowledgement happens, the B chain can facilitate transport of the A chain into the cytoplasm[2]. This association between the A and B chain is essential for toxicity[2] without it the Ricin would not be able to gain access to the cells organelles rendering it useless. Once the A chain gains entry into the cytosol its mechanism for attack of the ribosome is depurination of a single adenosine residue in a highly conserved portion within the large RNA of the cytoplasmic large ribosomal subunit[3] of eukaryotes; in human, the large cytoplasmic ribosomal RNA is called the 28S ribosomal RNA because of its sedimentation properties during ultracentrifugation. The nucleotide depurinated is located within a specific, conserved loop referred to as th 'sarcin-ricin loop'; the loop is critical for binding elongation factors during translation of messenger RNA to protein [4]. Depurination of the single adenosine nucleotide by the toxin results in the inhibition of protein synthesis.
3D structures of ricin
Updated December 2011
Ricin A chain (RTA)
1j1m, 1ift, 2aai, 1rtc – RTA
3lc9, 3mk9, 2vc4, 1uq4, 1uq5, 1obs, 3bjg, 3srp – RTA (mutant)
Ricin A chain binary complexes
3px8 – RTA preproricin + 7-carboxy-pterin
1br5, 1br6 - RTA + pterin derivative
3px9 - RTA preproricin + furanylmethyl-carbamoyl-pterin
3lc9, 3mk9, 2vc4, 1uq4, 1uq5, 1obs – RTA (mutant)
3hio – RTA + tetranucleotide
3ej5, 1il5 – RTA pyrimidine derivative
2p8n, 1ifs – RTA + adenine
2pjo, 2r2x – RTA + urea derivative
2r3d – RTA + acetamide
2vc3 - RTA (mutant) + acetate
1il3, 1il4, 1il9 – RTA + guanine derivative
1ifu, 1fmp – RTA + formycin
1obt - RTA (mutant) + AMP
1apg – RTA + RNA
Ricin B chain (RTB)
3nbc, 3nbd – CnRTB + lactose – Clitocybe nebularis
3nbe – CnRTB + lactose derivative
3phz – RTB + glycoside – Polyporus squamosus
Ricin A+B chains
3px8 – RTA + RTB + formycin monophosphate
3rjt - RTA + RTB + dinucleotide
See Also
References
- ↑ 1.0 1.1 1.2 Lord JM, Roberts LM, Robertus JD. Ricin: structure, mode of action, and some current applications. FASEB J. 1994 Feb;8(2):201-8. PMID:8119491
- ↑ 2.0 2.1 2.2 2.3 2.4 Montfort W, Villafranca JE, Monzingo AF, Ernst SR, Katzin B, Rutenber E, Xuong NH, Hamlin R, Robertus JD. The three-dimensional structure of ricin at 2.8 A. J Biol Chem. 1987 Apr 15;262(11):5398-403. PMID:3558397
- ↑ 3.0 3.1 Rapak A, Falnes PO, Olsnes S. Retrograde transport of mutant ricin to the endoplasmic reticulum with subsequent translocation to cytosol. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3783-8. PMID:9108055
- ↑ Holmberg L, Nygard O. Depurination of A4256 in 28 S rRNA by the ribosome-inactivating proteins from barley and ricin results in different ribosome conformations. J Mol Biol. 1996 May 31;259(1):81-94. PMID:8648651 doi:10.1006/jmbi.1996.0303
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