Toxicon. 2013 Feb 20. pii: S0041-0101(13)00062-7. doi: 10.1016/j.toxicon.2013.02.001. [Epub ahead of print]
Targeting ricin to the ribosome.
Source
Department of Plant Biology and Pathology, School of Environmental and Biological Sciences, Rutgers University, 59 Dudley Road, New Brunswick, NJ 08901-8520, USA.
Abstract
The plant toxin ricin is highly toxic for mammalian cells and is of concern for bioterrorism. Ricin belongs to a family of functionally related toxins, collectively referred to as ribosome inactivating proteins (RIPs), which disable ribosomes and halt protein synthesis. Currently there are no specific antidotes against ricin or related RIPs. The enzymatic subunit of ricin is an N-glycosidase that depurinates a universally conserved adenine residue within the sarcin/ricin loop (SRL) of the 28S rRNA. This depurination activity inhibits translation and its biochemistry has been intensively studied. Yet, recent developments paint a more complex picture of toxicity, with ribosomal proteins and cellular signaling pathways contributing to the potency of ricin. In particular, several studies have now established the importance of the ribosomal stalk structure in facilitating the depurination activity and ribosome specificity of ricin and other RIPs. This review highlights recent developments defining toxin-ribosome interactions and examines the significance of these interactions for toxicity and therapeutic intervention.
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