Lord / Hartley Toxic Plant Proteins

2010
ISBN: 978-3-642-12176-0
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band 18, 270 Seiten

Reihe: Plant Cell Monographs

Many plants produce enzymes collectively known as ribosome-inactivating proteins (RIPs). RIPs catalyze the removal of an adenine residue from a conserved loop in the large ribosomal RNA. The adenine residue removed by this depurination is crucial for the binding of elongation factors. Ribosomes modified in this way are no longer able to carry out protein synthesis. Most RIPs exist as single polypeptides (Type 1 RIPs) which are largely non-toxic to mammalian cells because they are unable to enter them and thus cannot reach their ribosomal substrate. In some instances, however, the RIP forms part of a heterodimer where its partner polypeptide is a lectin (Type 2 RIPs). These heterodimeric RIPs are able to bind to and enter mammalian cells. Their ability to reach and modify ribosomes in target cells means these proteins are some of the most potently cytotoxic poisons found in nature, and are widely assumed to play a protective role as part of the host plant's defenses. RIPs are able to further damage target cells by inducing apoptosis. In addition, certain plants produce lectins lacking an RIP component but which are also cytotoxic. This book focuses on the structure/function and some potential applications of these toxic plant proteins.

Autoren/Hrsg.

Lord, J. Michael

Hartley, Martin R.

Inhaltsverzeichnis

1;Editors;6
2;Preface;8
3;Contents;10
4;Evolution of Plant Ribosome-Inactivating Proteins;12
4.1;1 Introduction;12
4.2;2 General Overview of the Taxonomic Distribution of A and B Domains within the Viridiplantae;13
4.3;3 Overview of the Taxonomic Distribution of A and B Domains within the Magnoliophyta (Flowering Plants);15
4.3.1;3.1 ``Classical´´ Type 2 RIPs (AB proteins);15
4.3.2;3.2 Other Proteins with Ricin- Domains;16
4.4;4 Molecular Evolution of Type 2 RIPs;16
4.4.1;4.1 General Observations Concerning the Taxonomic Distribution of Type 2 RIPs and the Occurrence of Multiple Paralogs;16
4.4.2;4.2 Overall Phylogeny of Type 2 RIPs;17
4.4.3;4.3 Special Evolutionary Events: Gene Amplification and Generation of Type A and Type B Proteins from Genuine Type 2 RIPs;19
4.4.4;4.4 What is the Origin of Type 2 RIP Genes?;22
4.4.4.1;4.4.1 Origin of the B-hain;22
4.4.4.2;4.4.2 Origin of the A-hain;23
4.5;5 Molecular Evolution of Type 1 RIPs;23
4.5.1;5.1 Dicots and Monocots Other Than Poaceae;24
4.5.2;5.2 Poaceae Type 1 RIPs;27
4.5.2.1;5.2.1 O. sativa;27
4.5.2.2;5.2.2 Andropogoneae: Z. mays and Sorghum bicolor;28
4.5.2.3;5.2.3 Pooideae;29
4.5.2.4;5.2.4 Relationships between the RIPs from Poaceae and Other Seed Plants;29
4.6;6 What is the Relationship between Plant and Bacterial RIPs?;31
4.7;7 Chimeric RIPs Other Than Type 2 RIPs;31
4.7.1;7.1 JIP60 and Other Type AC Chimeric RIPs;31
4.7.2;7.2 Chimeric RIP with a C-erminal D Domain;34
4.8;8 Conclusions;34
4.9;References;36
5;RNA N-Glycosidase Activity of Ribosome-Inactivating Proteins;38
5.1;1 Introduction;38
5.2;2 Ricin as an RNA N-lycosidase;39
5.2.1;2.1 28S rRNA as the Target of Modification by Ricin and Other RIPs;39
5.2.2;2.2 RNA N-lycosidase Activity of Ricin A-hain;41
5.2.3;2.3 Other RIPs;42
5.2.4;2.4 Major Role of RNA in Protein Synthesis;42
5.3;3 Ribosomal Mechanisms Involving the Sarcin-icin Domain;43
5.3.1;3.1 Eukaryotic Translation Can Be Inhibited Strongly by Dysfunction of a Small Fraction of the Ribosome Population;43
5.3.2;3.2 Difference in the Modes of Action between a-arcin and Ricin;43
5.3.3;3.3 Substrate Specificity;44
5.3.4;3.4 Structure of the SRL;44
5.4;4 Ribosomal RNA Apurinic Site-pecific Lyase: Intrinsic Stability of the Ribosome;46
5.5;References;48
6;Enzymatic Activities of Ribosome-Inactivating Proteins;51
6.1;1 Introduction;51
6.2;2 Action of RIPs on Ribosomes and rRNA;52
6.2.1;2.1 Site of Modification by RIPs;52
6.2.2;2.2 Structural Requirements in Ribosomal RNA for RIP Action;53
6.3;3 Polynucleotide:Adenosine Glycosidase Activity;56
6.3.1;3.1 5 Cap-ndependent Activity;56
6.3.2;3.2 5 Cap-ependent Activity;57
6.4;4 DNA Lyase;59
6.5;5 Bifunctional Enzymes with RIP Activity in Which the Non-IP Activity Acts on Non-ucleic Acid Substrates;59
6.5.1;5.1 Lipase;59
6.5.2;5.2 Chitinase;60
6.5.3;5.3 Superoxide Dismutase;60
6.6;6 Conclusions;61
6.7;References;62
7;Type I Ribosome-Inactivating Proteins from Saponaria officinalis;65
7.1;1 Introduction;65
7.2;2 Saporin Multigene Family and Saporin Isoforms;66
7.3;3 Saporin Biochemical Features;68
7.3.1;3.1 Saporin Structure;68
7.3.2;3.2 Saporin Catalytic Activity;71
7.3.3;3.3 Residues Important for the Catalytic Activity;72
7.3.4;3.4 Interaction with the Ribosome;73
7.3.5;3.5 Saporin Inhibitors;74
7.4;4 Saporin Trafficking and Toxicity in Eukaryotic Cells;75
7.4.1;4.1 Subcellular Distribution of Saporin Isoforms in Soapwort Tissues;75
7.4.2;4.2 Saporin Biosynthesis and Role in Planta;76
7.4.3;4.3 Intoxication Pathways in Mammalian Cells;77
7.5;5 Heterologous Expression of Saporin and Saporin Fusion Toxins;80
7.6;6 Conclusions and Perspectives;82
7.7;References;82
8;Type 1 Ribosome-Inactivating Proteins from the Ombú Tree (Phytolacca dioica L.);89
8.1;1 Introduction;89
8.2;2 RIPs from P. dioica L.;90
8.2.1;2.1 Isolation of RIPs from Seeds and Leaves of P. dioica;92
8.2.2;2.2 Basic Characteristics of RIPs from Seeds and Leaves of P. dioica;92
8.2.3;2.3 Differential Seasonal and Age Expression in Leaves;97
8.2.4;2.4 Cellular Localization;98
8.2.5;2.5 Glycosylation of P. dioica RIPs;98
8.3;3 Enzymatic and Biological Characteristics;100
8.3.1;3.1 Neta-lycosidase and APG Activities;100
8.3.2;3.2 Toxicity to Mice;101
8.3.3;3.3 Immunotoxin;101
8.3.4;3.4 Cross-eactivity;102
8.3.5;3.5 Activity on Double-tranded pBR322 DNA;102
8.4;4 X-ay Crystal Structure of P. dioica RIPs;106
8.4.1;4.1 Atomic Resolution Studies of PD-4: A Reference RIP Structure;106
8.4.2;4.2 An Insight into the Active Site of PD-4: Tyr72 as a Substrate Carrier Through pi- Stacking Interactions with Aden;107
8.4.3;4.3 PD-1 and PD-4 -Two Homologous Proteins with Distinct Functional Properties;110
8.5;5 Concluding Remarks;111
8.6;References;112
9;Sambucus Ribosome-Inactivating Proteins and Lectins;117
9.1;1 Ribosome-nactivating Proteins;117
9.2;2 Occurrence and Structural Diversity of Sambucus Proteins;119
9.3;3 Similarity and Processing;122
9.4;4 Structure;126
9.5;5 Enzymic Activity;128
9.6;6 Toxicity to Cells and Animals;129
9.7;7 Interaction with Cells;130
9.8;8 Phylogenetic Relationship Among the RIPs and Lectins from Sambucus;132
9.9;9 Uses of the RIPs and Lectins From Sambucus;134
9.10;References;135
10;Ribosome-Inactivating Proteins from Abrus pulchellus;142
10.1;1 Introduction;142
10.2;2 Pulchellin Isoforms;145
10.3;3 The Heterologous Expression of Pulchellins;146
10.3.1;3.1 The Pulchellin A-hain;147
10.3.2;3.2 The Pulchellin B-hain;147
10.4;4 Pulchellin Endocytosis in Mammalian Cells;150
10.5;5 Structure of Pulchellin;151
10.6;6 Conclusion;153
10.7;References;154
11;Ribosome-Inactivating Proteins in Cereals;157
11.1;1 Introduction;157
11.2;2 Classification of RIPs;158
11.3;3 Applied Research on RIPs;159
11.4;4 Properties of Cereal RIPs;160
11.4.1;4.1 Rice RIPs;160
11.4.2;4.2 Wheat RIPs;161
11.4.3;4.3 Barley RIPs;161
11.4.4;4.4 Maize RIPs;162
11.5;5 Transgenic Plants Expressing RIPs;164
11.6;6 Conclusions;169
11.7;References;170
12;Ribosome Inactivating Proteins and Apoptosis;175
12.1;1 Introduction;175
12.2;2 Mechanism of Action of RIPs;176
12.3;3 Apoptosis;177
12.4;4 Ribosome Inactivating Proteins and Apoptosis;179
12.4.1;4.1 Activation of Intrinsic Pathway of Apoptosis by General Stress;180
12.4.2;4.2 Activation of the Extrinsic Pathway of Apoptosis;182
12.4.3;4.3 Impaired Balance Between and Pro-and Anti-poptotic Factors;183
12.4.4;4.4 Induction of Apoptosis in Response to Ribotoxic Stress;184
12.4.5;4.5 The Intrinsic Nuclease Activity of Toxins;187
12.4.6;4.6 Alternate Pathways;187
12.4.6.1;4.6.1 PARP Activation Resulting in NAD+Depletion;187
12.4.6.2;4.6.2 Down-egulation of Telomerase;188
12.4.6.3;4.6.3 Inhibition of Histone Deacetylase;188
12.4.6.4;4.6.4 Degradation of Cytoskeleton Proteins;189
12.4.6.5;4.6.5 Nitric Oxide-ediated Apoptosis Pathway;189
12.5;5 Conclusion;189
12.6;References;189
13;The Synthesis of Ricinus communis Lectins;198
13.1;1 Introduction;198
13.2;2 Ricin;199
13.2.1;2.1 Synthesis and Quality Control of Proricin;199
13.2.1.1;2.1.1 Synthesis and ER Translocation;200
13.2.1.2;2.1.2 Anterograde Trafficking;200
13.2.2;2.2 Ricin A Chain: ER Synthesis and Turnover in the Cytosol;203
13.2.3;2.3 Ricin B Chain: Synthesis and Quality Control;206
13.3;3 RCA 1;206
13.3.1;3.1 RCA Synthesis and Assembly;207
13.4;4 Concluding Remarks;207
13.5;References;207
14;How Ricin Reaches its Target in the Cytosol of Mammalian Cells;213
14.1;1 Introduction;213
14.2;2 Cytotoxicity Model;214
14.3;3 Cell Entry;215
14.3.1;3.1 Cell Surface Events Remain Cryptic;215
14.3.2;3.2 Retrograde Trafficking;215
14.3.3;3.3 Ricin Is Delivered to the ER;218
14.3.4;3.4 Ricin Is Reduced to its Constituent Chains in the ER;219
14.3.5;3.5 RTA Unfolds in the ER;219
14.3.6;3.6 Chaperone Interactions in the ER;221
14.3.7;3.7 The Dislocation Process for RTA Remains Mysterious;222
14.4;4 Recovery of Activity in the Cytosol;223
14.5;5 Conclusions;225
14.6;References;226
15;Ribosome-Inactivating Protein-Containing Conjugates for Therapeutic Use;231
15.1;1 Introduction ;231
15.2;2 Distribution;233
15.2.1;2.1 Enzymatic Activity;234
15.2.2;2.2 Toxicity;235
15.3;3 Properties of RIPs;236
15.3.1;3.1 Other Biological Properties;237
15.3.2;3.2 Possible Uses;237
15.3.3;3.3 Role in Nature;238
15.4;4 RIP-Based Immunotoxins;238
15.4.1;4.1 Chemical Immunotoxins;238
15.4.2;4.2 Recombinant Immunotoxins;239
15.4.3;4.3 In Vitro Cytotoxicity;241
15.4.4;4.4 Enhancement of Cytotoxicity;241
15.4.4.1;4.4.1 Lysosomotropic Amines and Carboxylic Ionophores;241
15.4.4.2;4.4.2 Ammonium Chloride (NH4Cl) ;242
15.4.4.3;4.4.3 Chloroquine;242
15.4.4.4;4.4.4 Other Lysosomotropic Amines (Methylamine, Amantadine);242
15.4.4.5;4.4.5 Carboxylic Ionophores;243
15.4.4.6;4.4.6 Antagonists of Ca++ Channels and Other Compounds3.4.6 Antagonists of Ca++ channels and other compounds;244
15.4.4.7;4.4.7 Verapamil and Its Derivatives;244
15.4.4.8;4.4.8 Perhexiline and Indolizines;245
15.4.4.9;4.4.9 Ricin B-Chain;245
15.4.4.10;4.4.10 Viruses;246
15.4.4.11;4.4.11 Saponins;246
15.5;5 Animal Studies;246
15.6;6 Ex Vivo Bone Marrow Purging with Immunotoxins;248
15.7;7 Clinical Studies;249
15.7.1;7.1 Hematologic Tumors;249
15.7.1.1;7.1.1 Hodgkin´s Lymphoma;250
15.7.1.2;7.1.2 Non-Hodgkin´s Lymphoma;250
15.7.1.3;7.1.3 Leukemia;251
15.7.1.4;7.1.4 Multiple Myeloma;252
15.7.1.5;7.1.5 Cutaneous Lymphoma;252
15.7.2;7.2 Cerebrospinal Fluid Spread of Tumors;252
15.7.3;7.3 Solid Tumors;252
15.7.3.1;7.3.1 Small-Cell Lung Cancer (SCLC);252
15.7.3.2;7.3.2 Bladder Cancer;253
15.7.3.3;7.3.3 Breast Tumors;253
15.7.3.4;7.3.4 Colon Carcinoma;253
15.7.3.5;7.3.5 Melanoma;254
15.8;8 Autoimmune Diseases;254
15.8.1;8.1 RA;254
15.8.2;8.2 SLE ;255
15.9;9 Other Applications;255
15.9.1;9.1 Corneal Opacification;255
15.10;10 Problems and Opportunities in the Future Development of Immunotoxins;255
15.10.1;10.1 Selection of Patients;255
15.10.2;10.2 Immunogenicity;256
15.10.3;10.3 Side Effects;257
15.11;11 Conclusions;258
15.12;References;259
16;Index;270