: Gregor Anderluh, Jeremy H. Lakey
: Gregor Anderluh, Jeremy H. Lakey
: Proteins Membrane Binding and Pore Formation
: Springer-Verlag
: 9781441963277
: Advances in Experimental Medicine and Biology
: 1
: CHF 173.90
:
: Nichtklinische Fächer
: English
: 172
: Wasserzeichen
: PC/MAC/eReader/Tablet
: PDF
Formation of transmembrane pores is a very effective way of killing cells. It is thus not surprising that many bacterial and eukaryotic toxic agents are pore-forming proteins. Pore formation in a target membrane is a complex process composed of several steps; proteins need to attach to the lipid membrane, possibly aggregate in the plane of the membrane and finally form a pore by inserting part of the polypeptide chain across the lipid bilayer. Structural information about toxins at each stage is indispensible for the biochemical and molecular biological studies that aim to - derstand how pores are formed at the molecular level. There are currently only two Staphylococcus aureus and hemolysin E from Escherichia coli. Therefore, what we know about these proteins was obtained over many years of intense experimentation. We have nevertheless, in the last couple of years, witnessed a significant rise in structural information on the soluble forms of pore-forming proteins. Surprisingly, many unexpected similarities with other proteins were noted, despite extremely low or insignificant sequence similarity. It appears that lipid membrane binding and formation of transmembrane channels is achieved in many cases by a limited repertoire of structures. This book describes how several of the important pore forming toxin families achieve membrane bi- ing and which structural elements are used for formation of transmembrane pores. Our contributors have thus provided the means for a comparative analysis of several unrelated families.

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 Page3
Copyright Page4
PREFACE5
ABOUT THE EDITORS...7
ABOUT THE EDITORS...8
PARTICIPANTS9
Table of Contents13
Chapter 1 Introduction18
Introduction18
Nomenclature19
Three-Dimensional Structures of Pore-Forming Proteins19
Pore-Forming Peptides19
a-PFTs20
B-PFTs22
Bcl-2 Proteins23
MACPF Superfamily23
CLICs23
Membrane Binding24
Oligomerization24
Common Features of Membrane Insertion25
a-PFPs25
B-PFTs25
CLICs26
Conclusion26
References27
Chapter 2 Energetics of Peptide and Protein Binding to Lipid Membranes31
The Lipid Bilayer Phase31
Hydrophobic Interactions32
Electrostatic Interactions34
Additivity between Electrostatic and Hydrophobic Interactions35
The Influence of Peptide and Protein Structure35
Specific Interactions36
Specificity: The Formation of Ordered Pores36
Promiscuity: Membrane-Permeabilization by Interfacial Activity38
Conclusion38
References39
Chapter 3 Membrane Association and Pore Formation by Alpha-Helical Peptides41
Introduction41
Alamethicin and Other Peptaibols41
Cationic Amphipathic Antimicrobial Peptides43
Membrane Proteins44
Conclusion44
References45
Chapter 4 Role of Membrane Lipids for the Activity of Pore Forming Peptides and Proteins48
Introduction48
Membrane Interfaces Are Ideal Binding Sites for Pore-Forming Peptides and Proteins49
General Effects of Negatively Charged Lipids51
Some Specific Roles of Lipids for Membrane Binding53
A Membrane Foldase Activity Configures Peptide and Protein Active Structures54
Structure Remodelling at the Membrane Interface54
The Lipid Membrane Controls Inter-Protein Interactions55
The Complex Membrane-Dependent Regulation of Bcl-2 Proteins55
Role of Lipids in the Formation and Stabilization of Pores56
The Latent Membrane Pores: Relatives of Pores Induced by Polypeptides?56
A Consensus View of Pore Formation Stressing the Role of Lipids58
Physical Properties of Polypeptide-Induced Pores Related to the Role of Lipids61
Surface Tension, Line Tension and the Stability of Membrane Pores61
Lipid-Driven Cooperativity: A Many-Body Effect Triggering Pore Formation61
The Elusive Role of Spontaneous Curvature: Classical and Nonclassical Effects63
Conclusion64
References65
Chapter 5 Cholesterol-Dependent Cytolysins73
Functional Studies on CDCs75
Membrane Binding by CDCs75
Pore Formation by CDCs77
Proteolipid Pores77
Oligomerisation—A Mechanism for Membrane Insertion78
Complex Effects of CDCs and Related Protiens79
Conclusion79
References80
Chapter 6 Laetiporus sulphureus Lectin and Aerolysin Protein Family84
Introduction84
Pore-Forming Hemolytic Lectins85
A New Member within the Aerolysin Family: The Crystal Structure of LSLa86
The N-Terminal Lectin Module87
The C-Terminal Pore-Forming Module88
Oligomeric State of Water-Soluble LSLa89
A Common Aerolysin-Like Pore-Forming Module Structure?90
L-Domains90
B-Domains92
Other New Members in the Aerolysin Family: Basic Aerolysin Pore-Forming Motifs?93
Conclusion95
References95
Chapter 7 Interfacial Interactions of Pore-Forming Colicins98
Introduction98
Structures99
Receptor Binding99
Translocation99
Crossing the Periplasm102
Inner Membrane Inserted Forms103
Conclusion104
References104
Chapter 8 Permeabilization of the Outer Mitochondrial Membrane by Bcl-2 Proteins108
Introduction108
The Structure of the Bcl-2 Proteins109
Structures of Water Soluble Forms109
Membrane-Associated Conformations111
Pore-Forming Properties of Bcl-2 Proteins113
Regulation of MOM Permeabilization by Bcl-2 Proteins115
Activation of Bcl-2 Proteins115
Inhibition by Antiapoptotic Bcl-2 Proteins116
Bcl-2 Interaction Networks Regulate Apoptosis116
Conclusion117
References117
Chapter 9 Molecular Mechanism of Sphingomyelin-Specific Membrane Binding and Pore Formation by Actinoporins123
Introduction123
Structural Properties of Actinoporins124
Actinoporins Specifically Bind Sphingomyelin as the First Step in Pore Formation124