Ricin

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==Physiology==
==Physiology==
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The mechanism deployed by Ricin to gain entry to a host cell uses the heterogenic properties given to the toxin. Firstly 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 fascilitate transport of the A chain into the cytoplasm<ref name="montfort" />. 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 cells organelles rendering it useless. Once the A chain gains entry into the cytosol its mechanism for attack of the [[Ribosome|ribosome]] is depurination of a single endenosine residue in large RNA of the [[Large Ribosomal Subunit of Haloarcula|large ribosomal subunit]]<ref name="rapak" />, which in humans is called the 28S ribosomal RNA because of its sedimentation properties during ultracentrifugation. Depurination of the ribosomal RNA by the poison in turn results in the inhibition of protein synthesis.
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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<ref name="montfort" />. 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 cells organelles rendering it useless. Once the A chain gains entry into the cytosol its mechanism for attack of the [[Ribosome|ribosome]] is depurination of a single adenosine residue in a highly conserved portion within the large RNA of the [[Large Ribosomal Subunit of Haloarcula|large ribosomal subunit]]<ref name="rapak" /> of eukaryotes, which in humans is called the 28S ribosomal RNA because of its sedimentation properties during ultracentrifugation. The nucleotide depurinated is located within a loop referred to as the the the <nowiki>'</nowiki>sarcin-ricin loop<nowiki>'</nowiki>, that is important for binding [[elongation factors]] during the course of [[Translation|translation]]. Depurination of the single adenosine nucleotide by the toxin results in the inhibition of protein synthesis.
==3D structures of ricin==
==3D structures of ricin==

Revision as of 13:29, 30 August 2011

Template:STRUCTURE 2r3d


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 large ribosomal subunit[3] of eukaryotes, which in humans is called the 28S ribosomal RNA because of its sedimentation properties during ultracentrifugation. The nucleotide depurinated is located within a loop referred to as the the the 'sarcin-ricin loop', that is important for binding elongation factors during the course of translation. Depurination of the single adenosine nucleotide by the toxin results in the inhibition of protein synthesis.

3D structures of ricin

Ricin A chain (RTA)

1j1m, 1ift, 2aai, 1rtc – RTA
3lc9, 3mk9, 2vc4, 1uq4, 1uq5, 1obs – 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, 2il5 – RTA pyrimidine derivative
2p8n, 1ifs – RTA + adenine
2pjo, 2r2x – RTA + urea derivative
2r3d – RTA + acetamide
2vc3 - RTA (mutant) + acetate
1il3, 2il4, 2il9 – RTA + guanine derivative
1ifu, 1fmp – RTA + formycin
1obt - RTA (mutant) + AMP
1apg – RTA + RNA

See Also

References

  1. ↑ 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. ↑ 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. ↑ 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
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