Ribosome‐inactivating proteins from plants: more than RNA N‐glycosidases?

Abstract

Many plants contain proteins that are capable of inactivating ribosomes and accordingly are called ribosome-inactivating proteins or RIPs. These typical plant proteins receive a lot of attention in biological and biomedical research because of their unique biological activities toward animal and human cells. In addition, evidence is accumulating that some RIPs play a role in plant defense and hence can be exploited in plant protection. To understand the mode of action of RIPs and to optimize their medical and therapeutical applications and their use as antiviral compounds in plant protection, intensive efforts have been made to unravel the enzymatic activities of RIPs and provide a structural basis for these activities. Though marked progress has been made during the last decade, the enzymatic activity of RIPs has become a controversial issue because of the concept that RIPs possess, in addition to their classical RNA N-glycosidase and polynucleotide:adenosine glycosidase activity, other unrelated enzymatic activities. Moreover, the presumed novel enzymatic activities, especially those related to diverse nuclease activities, are believed to play an important role in various biological activities of RIPs. However, both the novel enzymatic activities and their presumed involvement in the biological activities of RIPs have been questioned because there is evidence that the activities observed are due to contaminating enzymes. We offer a critical review of the pros and cons of the putative novel enzymatic activities of RIPs. Based on the available data, it is suggested that there is little conclusive evidence in support of the presumed activities and that in the past too little attention has been given to the purity of the RIP preparation. The antiviral activity and mode of action of RIPs in plants are discussed in view of their classical and presumed novel enzymatic activities.

The N-Glycosidase Activity of the Ribosome-inactivating Protein ME1 Targets Single-stranded Regions of Nucleic Acids Independent of Sequence or Structural Motifs

“…However, changes in RNA tertiary structure may explain the activity of certain RIPs on guanine, a nucleotide considered to be a minor substrate site on both ribosome and non-ribosomal substrates (1,21,24). Thus far, only ricin and PAP have been shown to have deguanylation activity (52), and recent experiments using highly purified RIPs have ruled out deguanylation activity for gelonin, momordin, PAP-S, and saporin-S6 (53). Our results indicate that ME 1 can only remove guanine residues from pap-h mRNA pretreated at 60°C.…”

Novel antibodies as anticancer agents

“…Among plant toxins, the most frequently employed for immunotoxins are ribosome inactivating proteins (RIPs). Most common RIPs are divided into two major groups: type 1 RIP, which is a single-chain protein, and type 2 RIP, which consists of an enzymatic subunit A, linked via disulfide bond to a B subunit bearing lectin properties (Barbieri et al, 1993;Peumans et al, 2001). Type 1 RIPs and the A subunit of type 2 RIPs is an RNA Nglycosidase that cleaves adenine molecules from ribosomal RNA, thus inactivating the ribosome in an irreversible manner.…”

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.…”