Ribosome-inactivating proteins: progress and problems

Abstract

Ribosome-inactivating proteins (RIPs), mostly from plants, are enzymes which depurinate rRNA, thus inhibiting protein synthesis. They also depurinate other polynucleotide substrates. The biological activity of RIPs is not completely clarified, and sometimes independent of the inhibition of protein synthesis. There are differences in the cytotoxicity of RIPs and, consequently, in their toxicity to animals. Some RIPs are potent toxins, the best known being ricin, a potential biological weapon. New toxins have recently been identified. RIPs cause apoptotic and necrotic lesions, and induce production of cytokines causing inflammation. RIPs are potentially useful in agriculture and medicine because (i) they have antiviral activity and (ii) they are used for the preparation of conjugates with antibodies ('immunotoxins') or other carriers, rendering them specifically toxic to the cell target of the carrier, which may be helpful in therapy. The distribution, mechanism of action and role in nature of RIPs are not completely understood, and we can expect several future developments in their practical application.

Evolution of Plant Ribosome-Inactivating Proteins

“…The issue of the molecular evolution of plant RIPs was already discussed in numerous research and review papers (Barbieri et al 1993;Peumans et al 2001;Van Damme et al 2001;Stirpe and Battelli 2006). Though several aspects of the overall evolution are fairly well understood, some important questions remain to be answered especially with respect to the origin of the RIP domain, the relationships between type 1 and type 2 RIPs, and the origin of the type 3 RIP.…”

Single-molecule investigations of the stringent response machinery in living bacterial cells

“…At the very same time, in vitro biochemical methods, however powerful when applied to other ribosome-associated enzymes, have so far failed to characterize these events as well. The original hopping model (10) was inferred within a very general conceptual framework that encompasses a broad range of ribosome-interacting enzymes, be it translational GTPases (11), ribosome-inactivating toxins (12), or ribosome RNA modification enzymes (13). Direct experimental evidence for hopping, for the synthesis of one ppGpp alarmone per one dissociation event, and also for the reaction being performed on the ribosome, is lacking (10).…”

Evaluation of Riproximin Binding Properties Reveals a Novel Mechanism for Cellular Targeting

“…Riproximin belongs to type II of the cytotoxic ribosome-inactivating proteins (RIPs) 3 (4). Several members of this family were investigated as potential antineoplastic agents, most prominently ricin.…”