Proteins (eBook)

Gregor Anderluh is Associate Professor of Biochemistry at the Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia. He and his coworkers are studying protein-membrane interactions and how cellular membranes are damaged by proteins. He is a director of the Infrastuctural Centre for Surface Plasmon Resonance at the University of Ljubljana, where they study molecular interactions and are developing novel approaches on how to study protein binding to membranes. He received his PhD in Biology from University of Ljubljana and did his Postdoctoral at University of Newcastle, United Kingdom. Jeremy Lakey is Professor of Structural Biochemistry at the Institute for Cell and Molecular Biosciences, University of Newcastle, UK and runs an academic research group based loosely on the theme of protein biophysical chemistry with interests in protein toxins, membranes and bionanotechnology. Following a first degree in Zoology, Jeremy completed a PhD in Membrane Biophysics at the University of East Anglia UK, followed by periods at the Centre de Biophysique Moléculaire, Orléans, France; EMBL, Heidelberg, Germany and the EPFL , Lausanne Switzerland. He is currently an editor of the Biochemical Journal and member of the facility access panel for the ISIS pulsed neutron source, UK.

Title Page 3
Copyright Page 4
PREFACE 5
ABOUT THE EDITORS... 7
ABOUT THE EDITORS... 8
PARTICIPANTS 9
Table of Contents 13
Chapter 1 Introduction 18
Introduction 18
Nomenclature 19
Three-Dimensional Structures of Pore-Forming Proteins 19
Pore-Forming Peptides 19
a-PFTs 20
B-PFTs 22
Bcl-2 Proteins 23
MACPF Superfamily 23
CLICs 23
Membrane Binding 24
Oligomerization 24
Common Features of Membrane Insertion 25
a-PFPs 25
B-PFTs 25
CLICs 26
Conclusion 26
References 27
Chapter 2 Energetics of Peptide and Protein Binding to Lipid Membranes 31
The Lipid Bilayer Phase 31
Hydrophobic Interactions 32
Electrostatic Interactions 34
Additivity between Electrostatic and Hydrophobic Interactions 35
The Influence of Peptide and Protein Structure 35
Specific Interactions 36
Specificity: The Formation of Ordered Pores 36
Promiscuity: Membrane-Permeabilization by Interfacial Activity 38
Conclusion 38
References 39
Chapter 3 Membrane Association and Pore Formation by Alpha-Helical Peptides 41
Introduction 41
Alamethicin and Other Peptaibols 41
Cationic Amphipathic Antimicrobial Peptides 43
Membrane Proteins 44
Conclusion 44
References 45
Chapter 4 Role of Membrane Lipids for the Activity of Pore Forming Peptides and Proteins 48
Introduction 48
Membrane Interfaces Are Ideal Binding Sites for Pore-Forming Peptides and Proteins 49
General Effects of Negatively Charged Lipids 51
Some Specific Roles of Lipids for Membrane Binding 53
A Membrane Foldase Activity Configures Peptide and Protein Active Structures 54
Structure Remodelling at the Membrane Interface 54
The Lipid Membrane Controls Inter-Protein Interactions 55
The Complex Membrane-Dependent Regulation of Bcl-2 Proteins 55
Role of Lipids in the Formation and Stabilization of Pores 56
The Latent Membrane Pores: Relatives of Pores Induced by Polypeptides? 56
A Consensus View of Pore Formation Stressing the Role of Lipids 58
Physical Properties of Polypeptide-Induced Pores Related to the Role of Lipids 61
Surface Tension, Line Tension and the Stability of Membrane Pores 61
Lipid-Driven Cooperativity: A Many-Body Effect Triggering Pore Formation 61
The Elusive Role of Spontaneous Curvature: Classical and Nonclassical Effects 63
Conclusion 64
References 65
Chapter 5 Cholesterol-Dependent Cytolysins 73
Functional Studies on CDCs 75
Membrane Binding by CDCs 75
Pore Formation by CDCs 77
Proteolipid Pores 77
Oligomerisation—A Mechanism for Membrane Insertion 78
Complex Effects of CDCs and Related Protiens 79
Conclusion 79
References 80
Chapter 6 Laetiporus sulphureus Lectin and Aerolysin Protein Family 84
Introduction 84
Pore-Forming Hemolytic Lectins 85
A New Member within the Aerolysin Family: The Crystal Structure of LSLa 86
The N-Terminal Lectin Module 87
The C-Terminal Pore-Forming Module 88
Oligomeric State of Water-Soluble LSLa 89
A Common Aerolysin-Like Pore-Forming Module Structure? 90
L-Domains 90
B-Domains 92
Other New Members in the Aerolysin Family: Basic Aerolysin Pore-Forming Motifs? 93
Conclusion 95
References 95
Chapter 7 Interfacial Interactions of Pore-Forming Colicins 98
Introduction 98
Structures 99
Receptor Binding 99
Translocation 99
Crossing the Periplasm 102
Inner Membrane Inserted Forms 103
Conclusion 104
References 104
Chapter 8 Permeabilization of the Outer Mitochondrial Membrane by Bcl-2 Proteins 108
Introduction 108
The Structure of the Bcl-2 Proteins 109
Structures of Water Soluble Forms 109
Membrane-Associated Conformations 111
Pore-Forming Properties of Bcl-2 Proteins 113
Regulation of MOM Permeabilization by Bcl-2 Proteins 115
Activation of Bcl-2 Proteins 115
Inhibition by Antiapoptotic Bcl-2 Proteins 116
Bcl-2 Interaction Networks Regulate Apoptosis 116
Conclusion 117
References 117
Chapter 9 Molecular Mechanism of Sphingomyelin-Specific Membrane Binding and Pore Formation by Actinoporins 123
Introduction 123
Structural Properties of Actinoporins 124
Actinoporins Specifically Bind Sphingomyelin as the First Step in Pore Formation 124
Flexibility of the N-Terminal Region Is Required for Pore Formation 128
Pore Formation Involves Nonlamellar Lipid Structures 128
Similarity to Other Proteins 129
Conclusion 130
References 130
Chapter 10 Hemolysin E (HlyE, ClyA, SheA) and Related Toxins 133
Introduction 133
Regulation of hlyE Expression 133
Structural Studies on HlyE 134
Crystal Structure of the Water-Soluble Form 134
Oligomerization in Solution 135
Electron Microscopy of HlyE Pores 136
Models of the Pore Structure 137
Crystal Structure of the Pore Form 138
Process of Membrane Insertion 139
HlyE Secretion and Exploitation in Vaccine Development and Tumour Targeting 140
HlyE-Like Toxins from Bacillus cereus 140
Conclusion 141
References 142
Chapter 11 Pore Formation by Cry Toxins 144
Introduction 144
Mechanism of Action of Cry Toxins 148
Solubilization and Proteolytic Activation of Cry Toxins 149
Binding Interaction with Receptors 149
Role of Cry Toxin-Receptor Interaction in Toxicity 152
Oligomerization of Cry Toxins 152
Pore Formation 153
Synergism between Cry and Cyt Toxins 154
Conclusion 155
References 155
Chapter 12 Role of Heparan Sulfates and Glycosphingolipids in the Pore Formation of Basic Polypeptides of Cobra Cardiotoxin 160
Introduction 160
Amphiphilic Properties of Three-Fingered CTXs 161
Diverse Targets of CTX Homologues 162
CTX A3 Pores in Sulfatide Containing Membranes 162
Pore Formations also Trigger Endocytosis 162
HS Facilitate Cell Surface Retention of CTXs 163
HS Stabilizes Membrane Bound Form of CTX 163
From HS to Membrane Sulfatides 163
Peripheral Binding Modes 163
Lipid Headgroup Conformational Change to Facilitate CTX Insertion 163
Pore Dynamics 165
Conclusion 165
References 165
Chapter 13 Amyloid Peptide Pores and the Beta Sheet Conformation 167
Introduction 168
Aggregation and Fibril Formation: Hallmark of Amyloid Peptides 169
Interaction of Amyloid Peptides and Membranes during Ion Channel Formation 171
Amyloid-Beta Peptide 171
Amylin (or Islet Amyloid Polypeptide, IAPP) 174
Prion Peptides 175
Alpha-Synuclein 176
Similarities between Pore-Forming Toxins and Amyloid Pores 176
B-Sheet Peptide Pores 177
Mechanism of Ion Channel Formation by Beta Sheet Peptides 179
Conclusion 181
References 181
Index 185