Toxic Plant Proteins [1 ed.] 3642121756, 9783642121753

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Plant Cell Monographs Volume 18 Series Editor: David G. Robinson Heidelberg, Germany

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J. Michael Lord

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Martin R. Hartley

Editors

Toxic Plant Proteins

Editors Dr. J. Michael Lord University of Warwick Dept. Biological Sciences CV4 7AL Coventry United Kingdom [email protected]

Dr. Martin R. Hartley University of Warwick Dept. Biological Sciences CV4 7AL Coventry United Kingdom [email protected]

Series Editor Professor Dr. David G. Robinson Ruprecht-Karls-University of Heidelberg Heidelberger Institute for Plant Sciences (HIP) Department Cell Biology Im Neuenheimer Feld 230 69120 Heidelberg Germany

ISSN 1861-1370 e-ISSN 1861-1362 ISBN 978-3-642-12175-3 e-ISBN 978-3-642-12176-0 DOI 10.1007/978-3-642-12176-0 Springer Heidelberg Dordrecht London New York Library of Congress Control Number: 2010929802 # Springer-Verlag Berlin Heidelberg 2010 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer. Violations are liable to prosecution under the German Copyright Law. The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Cover design: WMXDesign GmbH, Heidelberg, Germany Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)

Editors

Mike Lord studied Biochemistry at the University of Salford, UK, and completed his PhD at the University of Bradford, UK, in 1970. From 1970 to 1972 he worked at the University of California at Santa Cruz as a postdoctoral researcher. He returned to the UK in 1972 as a postdoctoral researcher at the University of Leicester, from where he moved to the University of Bradford as a Lecturer in 1973. He transferred to the University of Warwick as a Reader in Cell Biology in 1982, and he was appointed as Full Professor in Molecular Cell Biology there in 1988. His research interests have focussed on how protein toxins, such as the ribosome-inactivating protein ricin, enter and intoxicate mammalian cells.

Martin Hartley studied Botany at Imperial College, London, and completed his PhD there in 1970 in Plant Molecular Biology. He was appointed to the University of Warwick in 1970 where he worked on various molecular aspects of chloroplast development, including the biogenesis of chloroplast ribosomes. In 1987, he became interested in the action of ribosome-inactivating proteins on ribosomes and the physiological rationale for the production of ribosomeinactivating proteins by plants.

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Preface

Ribosome-inactivating proteins (RIPs) are a diverse group of proteins with an RNA N-glycosidase activity that irreversibly inactivates ribosomes through an active site – the RIP domain – that is unique. They are widely distributed among higher plants and a few species of bacteria, and in both kingdoms, the enzymatically active protein (the A chain) has become fused to a lectin or ceramide-binding B-chain giving rise to A–B toxins that are among the most potent cytotoxic agents known. Although there is very good evidence that these AB toxins have evolved to fulfil their toxic roles, it is only for the bacterial toxins Shiga toxin (from Shigella dysenteriae, responsible for outbreaks of bacillary dysentry) and the related Shiga-like toxin (from certain enterohemorrhagic strains of Escherichia coli) that their biological roles are known with certainty. For plant toxic lectins, such as ricin from the seeds of Ricinus communis, the biological role is less clearly understood. Many plants produce single-chain RIPs equivalent to the A chain of the toxic lectins. These are mainly active on their own (conspecific) ribosomes, are secreted into the apoplast, and have been postulated to have an anti-viral role, possibly by depurinating capped viral RNAs. In the Poaceae, they are cytosolic proteins and could be involved in the senescence of tissues/organs, as in the case of the wheat coleoptile. RIPs have attracted the attention of researchers from several different backgrounds. Those interested in ribosome structure and function have studied the role played by the domain in 28S rRNA upon which RIPs act. Cell biologists have used ricin as a model for understanding retrograde transport and membrane dislocation processes in animal cells, which has led to the possibility of using disarmed versions of ricin to deliver fused peptides into cells, leading to MHC class 1-restricted antigen presentation and the development of novel vaccination strategies. There has been considerable interest in using the catalytic chains of RIPs as the toxic moiety of immunotoxins directed against cancer cells. Neurobiologists have used the specificity of uptake afforded by certain neuropeptides to use neuropeptide-RIP fusions to ablate cells of the CNS. Plant biotechnologists are attempting to use RIPs to engineer plants to resist attack by pathogens.

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Preface

The last publication of a collection of articles on RIPs was in 2004 to mark the retirement of Fiorenzo Stirpe, one of pioneers in RIP research (Mini Reviews in Medicinal Chemistry 4:461–595). Significant advances have been made in the past 6 years and we feel that it is both timely and appropriate that this monograph should convey some of the developments that have taken place on this interesting, but to some extent enigmatic, class of proteins. January 2010

J. Michael Lord Martin R. Hartley

Contents

Evolution of Plant Ribosome-Inactivating Proteins . . . . . . . . . . . . . . . . . . . . . . . . . 1 Willy J. Peumans and Els J.M. Van Damme RNA N-Glycosidase Activity of Ribosome-Inactivating Proteins . . . . . . . . . 27 Kazuyuki Takai, Tatsuya Sawasaki, and Yaeta Endo Enzymatic Activities of Ribosome-Inactivating Proteins . . . . . . . . . . . . . . . . . . 41 Martin R. Hartley Type I Ribosome-Inactivating Proteins from Saponaria officinalis . . . . . . . 55 Alessio Lombardi, Richard S. Marshall, Carmelinda Savino, Maria Serena Fabbrini, and Aldo Ceriotti Type 1 Ribosome-Inactivating Proteins from the Ombu´ Tree (Phytolacca dioica L.) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 Augusto Parente, Rita Berisio, Angela Chambery, and Antimo Di Maro Sambucus Ribosome-Inactivating Proteins and Lectins . . . . . . . . . . . . . . . . . . . 107 Jose´ Miguel Ferreras, Lucı´a Citores, Rosario Iglesias, Pilar Jime´nez, and Toma´s Girbe´s Ribosome-Inactivating Proteins from Abrus pulchellus . . . . . . . . . . . . . . . . . . . 133 Ana Paula Ulian Arau´jo, Priscila Vasques Castilho, and Leandro Seiji Goto Ribosome-Inactivating Proteins in Cereals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149 Carlotta Balconi, Chiara Lanzanova, and Mario Motto Ribosome Inactivating Proteins and Apoptosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167 Deepa Sikriwal and Janendra K. Batra

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Contents

The Synthesis of Ricinus communis Lectins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191 Lorenzo Frigerio and Lynne M. Roberts How Ricin Reaches its Target in the Cytosol of Mammalian Cells . . . . . . 207 Robert A. Spooner, Jonathan P. Cook, Shuyu Li, Paula Pietroni, and J. Michael Lord Ribosome-Inactivating Protein-Containing Conjugates for Therapeutic Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225 Giulio Fracasso, Fiorenzo Stirpe, and Marco Colombatti Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265

Evolution of Plant Ribosome-Inactivating Proteins Willy J. Peumans and Els J.M. Van Damme

Abstract This contribution presents an updated analysis of the evolution of ribosome-inactivating proteins (RIPs) in plants. All evidence suggests that an ancestor of modern seed plants developed the RIP domain at least 300 million years ago. This ancestral RIP domain gave rise to a direct lineage of type 1 RIPs (i.e., primary type 1 RIPs) still present today in many monocots and at least one dicot. In a later stage, a plant succeeded in fusing the RIP domain to a duplicated ricin-B domain acquired from a bacterium. The resulting ancestral type 2 RIP gave rise to all modern type 2 RIPs and by domain deletion, to different lines of “secondary” type 1 RIPs and ricin-B type lectins. In the recent past, at least three other domain fusions took place in the Poaceae family, whereby type AC1 (type 3), type AC2, and type AD chimeric forms were generated.

1 Introduction Plant ribosome-inactivating proteins (RIPs) are a fairly extended and heterogeneous family of proteins characterized by the presence of a domain equivalent to the toxic A-chain of ricin (or A-subunit of the bacterial Shiga toxins). Basically, the plant RIPs can be subdivided into holoenzymes and chimero-enzymes. Holoenzymes or type 1 RIPs consist solely of a RIP domain whereas the chimero-enzymes are built up of an N-terminal RIP domain linked (at least in the gene) to an unrelated C-terminal domain. Depending on the nature of the latter chain, the chimeric forms are referred to as type 2 RIPs (with a lectinic B-chain) and type 3 RIPs

W.J. Peumans and E.J.M. Van Damme (*) Laboratory of Biochemistry and Glycobiology, Department of Molecular Biotechnology, Ghent University, Coupure Links 653, 9000 Ghent, Belgium e-mail: [email protected]

J.M. Lord and M.R. Hartley (eds.), Toxic Plant Proteins, Plant Cell Monographs 18, DOI 10.1007/978-3-642-12176-0_1, # Springer-Verlag Berlin Heidelberg 2010

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W.J. Peumans and E.J.M. Van Damme

(with an unidentified C-terminal domain). Both type 1 and type 2 RIPs are quite common in plants whereas hitherto only a single type 3 RIP has been isolated and characterized, namely the barley JIP60 (Chaudhry et al. 1994). However, recent genome and transcriptome data revealed the occurrence of homologs in some other Poaceae. Moreover, there is also evidence for yet another chimeric form in rice and Brachypodium distachyon. Since none of these “putative novel” RIPs has been studied at the biochemical level, it is precocious to introduce a new nomenclature. Therefore, JIP60 and its homologs will be referred to as type AC proteins, and the additional form found in rice and Brachypodium as type AD proteins, to emphasize the fact that they possess a different C-terminal domain. 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. One of the major problems encountered in the study of the evolution and phylogeny concerns the limited number of sequences and the patchy taxonomic distribution of plant RIPs. Fortunately, the wealth of information provided by genome and transcriptome sequencing programs allows composing a more detailed overview of the occurrence of RIPs in plants and reassessing the interrelationships between the different subgroups. Moreover, the eventual origin of the RIP domain itself as well as the B-chain of type 2 RIPs could also be revised using the sequence information made available for bacteria and eukaryotes other than plants. This contribution aims to make an updated comprehensive analysis of the overall evolution of plant RIPs. Therefore, an as-complete-as-possible set of sequences was retrieved from the publicly accessible databases and subsequently subjected to a preliminary phylogenetic analysis (using CLUSTALW). Considering the limitations of this method, the results should be interpreted with care. However, the outlines of the analyses give a fairly accurate idea and place the overall evolution of RIPs in a novel perspective. Moreover, the data generated here provide a firm basis for an in-depth phylogenetic analysis with a more performing program.

2 General Overview of the Taxonomic Distribution of A and B Domains within the Viridiplantae According to the data published in previous research and review papers, the occurrence within the Viridiplantae of both the RIP and the ricin-B domain is confined to the Magnoliophyta (flowering plants) (Van Damme et al. 1998; 2001). To check whether these domains possibly occur in other taxa, a comprehensive analysis of the publicly accessible databases was made. BLAST searches (using

Evolution of Plant Ribosome-Inactivating Proteins

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different type 1 and type 2 RIP sequences1 as queries) in the completed genomes of Chlamydomonas reinhardtii, Chlorella sp., Micromonas sp., Ostreococcus sp., and Volvox carteri yielded no positive hits indicating, though not proving, that Chlorophyta (green algae) genomes acquired neither the RIP nor the ricin-B domain. Within the Embryophyta, proteins/genes with a RIP domain are apparently confined to the Spermatophyta (seed plants). No A domain could be identified, indeed, in any member of the Anthocerotophyta, Bryophyta, Marchantiophyta, or Euphyllophyta other than Spermatophyta. Though, due to the limited sequence information, one cannot draw definitive conclusions regarding the possible occurrence of this domain in these major taxonomic groups, the apparent absence of the RIP domain in the completed genomes of the moss Physcomitrella patens and the club moss Selaginella moellendorffii is certainly indicative. Contrary to the A domain, there is compelling evidence of the expression of proteins with a typical ricin-B domain in the liverwort Marchantia polymorpha. Analysis of the transcriptome database revealed that thalli and sexual organs of M. polymorpha express a set of at least three different proteins comprising two in tandem arrayed ricin-B domains (and hence can be considered the equivalent of the B-chain of a type 2 RIP). One of these expressed proteins has -apart from the N-terminal Met residue- exactly the same sequence as the N-terminus of a galactose-binding lectin isolated from thallus tissue (EVD unpublished results), which leaves no doubt that this liverwort actually expresses a carbohydrate-binding protein of the ricin-B family. It should be noted here that the purified lectin is synthesized without signal peptide and undergoes, apart from the removal of the methionine, no processing at its N-terminus. This implies that the Marchantia lectins are unlike all other documented plant lectins of the ricin-B family (which are synthesized with a signal peptide and follow the secretory pathway) (Van Damme et al. 2001). Marchantia lectins are synthesized on free ribosomes in the cytoplasm and accordingly destined to reside in the cytoplasmic and/or nuclear compartment. Hitherto, all purified plant RIPs and cloned plant RIP genes were obtained from Magnoliophyta (flowering plants). No homologs were isolated from or identified in any other seed plant. Transcriptome analyses also yielded no evidence of the expression of RIP genes in Coniferophyta (approximately 800,000 entries), Cycadophyta (22,000 entries), and Ginkgophyta (21,000 entries). In contrast, a recently deposited transcriptome database of Gnetum gnemon (10,700 entries) contains a set of three expressed sequence tags (ESTs) encoding two different type 2 RIPs. The latter finding is important because it demonstrates for the first time the occurrence of RIP genes in a seed plant outside the flowering plants. Taking into consideration the very large number of deposited EST sequences (about 800,000 in total) of different Pinus and Picea species, it seems unlikely that RIP genes are present in the genome of most modern Coniferophyta. Due to the

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Sequences of all RIPs used in this study can be retrieved from: http://www.molecularbiotechnology. ugent.be/publications/VanDamme2010A/.

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W.J. Peumans and E.J.M. Van Damme

relatively small number of entries no such conclusion can be drawn yet for the Cycadophyta (22,000 entries) and Ginkgophyta (21,000 entries). Comprehensive BLAST searches of plant transcriptome databases yielded several sequences encoding proteins consisting of a single ricin-B domain (i.e., corresponding to one half of the B-chain of type 2 RIPs). At first sight, the identification of these proteins was exciting because it could give valuable hints with regard to the origin of the B-chain of type 2 RIPs. However, a closer examination indicated that these sequences are not encoded by the plant genome but by a contaminating fungus or other eukaryotic symbiont/parasite. For example, a strongly conserved protein expressed in roots of wheat and poplar, and stolons of potato turns out to be 94% identical to a large set (>250) of ESTs present in the transcriptome of Hartmannella vermiformis (a protozoan belonging to the Euamoebida). Hence, it is almost certain that the sequences encoding these “root-specific” proteins are derived from a contaminating amoeba.

3 Overview of the Taxonomic Distribution of A and B Domains within the Magnoliophyta (Flowering Plants) 3.1

“Classical” Type 2 RIPs (AB proteins)

Hitherto, only a relatively small set of type 2 RIPs (