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Proteins By Gregor Anderluh

Proteins by Gregor Anderluh

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Formation of transmembrane pores is a very effective way of killing cells. 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.

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Proteins Summary

Proteins: Membrane Binding and Pore Formation by Gregor Anderluh

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.

About Gregor Anderluh

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 Moleculaire, Orleans, 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.

Table of Contents

1. Introduction Susanne C. Feil, Galina Polekhina, Michael A. Gorman and Michael W. Parker Abstract Introduction Nomenclature Three?Dimensional Structures of Pore?Forming Proteins Membrane Binding Oligomerization Common Features of Membrane Insertion Conclusion 2. Energetics of Peptide and Protein Binding to Lipid Membranes William C. Wimley Abstract The Lipid Bilayer Phase Hydrophobic Interactions Electrostatic Interactions Additivity between Electrostatic and Hydrophobic Interactions The Influence of Peptide and Protein Structure Specific Interactions Specificity: The Formation of Ordered Pores Promiscuity: Membrane?Permeabilization by Interfacial Activity Conclusion 3. Membrane Association and Pore Formation by Alpha?Helical Peptides Burkhard Bechinger Abstract Introduction Alamethicin and Other Peptaibols Cationic Amphipathic Antimicrobial Peptides Membrane Proteins Conclusion 4. Role of Membrane Lipids for the Activity of Pore Forming Peptides and Proteins Gustavo Fuertes, Diana Gimenez, Santi Esteban?Martin, Ana J. Garcia?Saez, Orlando Sanchez and Jesus Salgado Abstract Introduction Membrane Interfaces Are Ideal Binding Sites for Pore?Forming Peptides and Proteins A Membrane Foldase Activity Configures Peptide and Protein Active Structures Role of Lipids in the Formation and Stabilization of Pores Physical Properties of Polypeptide?Induced Pores Related to the Role of Lipids Conclusion 5. Cholesterol?Dependent Cytolysins Robert J.C. Gilbert Abstract Functional Studies on CDCs Membrane binding by CDCs Pore Formation by CDCs Proteolipid Pores Oligomerisation- A Mechanism for Membrane Insertion Complex Effects of CDCs and Related Protiens Conclusion 6. Laetiporus sulphureus Lectin and Aerolysin Protein Family Jose Miguel Mancheno, Hiroaki Tateno, Daniel Sher and Irwin J. Goldstein Abstract Introduction Pore?Forming Hemolytic Lectins A New Member within the Aerolysin Family: The Crystal Structure of LSLa Oligomeric State ofWater?Soluble LSLa A Common Aerolysin?Like Pore?Forming Module Structure? Other New Members in the Aerolysin Family: Basic Aerolysin Pore?Forming Motifs? Conclusion 7. Interfa cial Interactions of Pore-Forming Colicins Helen Ridley, Christopher L. Johnson and Jeremy H. Lakey Abstract Introduction Structures Receptor Binding Translocation Crossing the Periplasm Inner Membrane Inserted Forms Conclusion 8. Permeabilization of the Outer Mitochondrial Membrane by Bcl?2 Proteins Ana J. Garcia?Saez, Gustavo Fuertes, Jacob Suckale and Jesus Salgado Abstract Introduction The Structure of the Bcl?2 Proteins Pore?Forming Properties of Bcl?2 Proteins Regulation of MOM Permeabilization by Bcl?2 Proteins Conclusion 9. Molecular Mechanism of Sphingomyelin?Specific Membrane Binding and Pore Formation by Actinoporins Biserka Bakra? and Gregor Anderluh Abstract Introduction Structural Properties of Actinoporins Actinoporins Specifically Bind Sphingomyelin as the First Step in Pore Formation Flexibility of the N?Terminal Region is Required for Pore Formation Pore Formation Involves Nonlamellar Lipid Structures Similarity to Other Proteins Conclusion 10. Hemolysin E (HlyE, ClyA, SheA) and Related Toxins Stuart Hunt, Jeffrey Green and Peter J. Artymiuk Abstract Introduction Regulation of hlyE Expression Structural Studies on HlyE Process of Membrane Insertion HlyE Secretion and Exploitation in Vaccine Development and Tumour Targeting HlyE?Like Toxins from Bacillus cereus Conclusion 11. Pore formation by Cry toxins Mario Soberon, Liliana Pardo, Carlos Munoz?Garay, Jorge Sanchez, Isabel Gomez, Helena Porta and Alejandra Bravo Abstract Introduction Mechanism of Action of Cry Toxins Solubilization and Proteolytic Activation of Cry toxins Binding Interaction with Receptors Role of Cry toxin?Receptor Interaction in Toxicity Oligomerization of Cry toxins Pore formation Synergism between Cry and Cyt toxins Conclusion 12. Role of Hepa ran Sulfa tes and

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Proteins: Membrane Binding and Pore Formation by Gregor Anderluh
Springer-Verlag New York Inc.
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