Ricin
IntroductionIntroduction
Ricin is a potent cytotoxin that is synthesized in the endosperm cells of maturing Riccinus seeds(1). Ricin belongs to a small multi gene family(2) that is composed of eight members. It is also important to mention that Ricin is classified as a type II heterodimeric Ribosome Inactivatiing protein(1).
StructureStructure
is a heterodimer that consists of a 32,000 Dalton A chain glycoprotein linked by a disulfide bond to a 32,000 Dalton 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(2) that binds to galactose-containing surface receptors(3).
PhysiologyPhysiology
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(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 endenosine residue in 28S Ribosomal RNA(3) and this inhibits protein synthesis
3D structures of ricin3D structures of ricin
Ricin A chain (RTA)Ricin A chain (RTA)
1j1m, 1ift, 2aai, 1rtc – RTA
3lc9, 3mk9, 2vc4, 1uq4, 1uq5, 1obs – RTA (mutant)
Ricin A chain binary complexesRicin 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
ReferencesReferences
1. Lord, Michael J., Roberts, Lynne M., Robertus, Jon D. Ricin: structure, mode of action, and some current applications. The FSEB journal. Vol 8. 1994. 2. Ernst, Stephen R., Hamlin, Ron., Katsen, Betsy., Montfort, William., Monzingo, Arthur F., Robertus, Jon D., Rutenbur, Earl., Villafranca, Jesus E., Xuong, Nuyhen H. The Three Dimensional Structure of Ricin at 2.8 Angstrom. The Journal of Biological Chemistry. Vol 262, No 11, pp. 5398-5403.1987. 3. Falnes, Pal., Olsnes, Sjur., Rapak, Andrzej. Retrograde Transport of Mutant Ricin to the Endoplasmic Recticulum with subsequent translocation to Cytosol. Cell Biology, Vol 94, pp. 3783-3788. 1997.