Fischer Viral Membrane Proteins: Structure, Function, and Drug Design

1. Auflage 2007
ISBN: 978-0-387-28146-9
Verlag: Springer US
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band 1, 292 Seiten

Reihe: Protein Reviews

In Viral Membrane Proteins: Structure, Function, and Drug Design, Wolfgang Fischer summarizes the current structural and functional knowledge of membrane proteins encoded by viruses. In addition, contributors to the book address questions about proteins as potential drug targets. The range of information covered includes signal proteins, ion channels, and fusion proteins. This book has a place in the libraries of researchers and scientists in a wide array of fields, including protein chemistry, molecular biophysics, pharmaceutical science and research, bioanotechnology, molecular biology, and biochemistry.

Autoren/Hrsg.

Fischer, Wolfgang B.

Inhaltsverzeichnis

1;Contents;6
2;List of Contributors;14
3;Preface;17
4;Part I Membrane Proteins from Plant Viruses;19
4.1;Membrane Proteins in Plant Viruses;20
4.1.1;1. Introduction;20
4.1.2;2. Survey of Transmembrane Proteins in Plant Viruses;20
4.1.3;3. Cell-to-Cell Movement Proteins;21
4.1.4;4. Replication Proteins;26
4.1.5;5. Proteins Involved in Transmission by Vectors;27
4.1.6;6. Other Membrane Proteins;30
4.1.7;7. Conclusions;31
4.1.8;Acknowledgments;31
4.1.9;References;31
4.2;Structure and Function of a Viral Encoded K+ Channel;37
4.2.1;1. Introduction;37
4.2.2;2. K+ Channels are Highly Conserved Proteins with Important Physiological Functions;38
4.2.3;3. Structural Aspects of Viral K+ Channel Proteins as Compared to those from Other Sources;38
4.2.4;4. The Short N-Terminus is Important for Kcv Function;40
4.2.5;5. Functional Properties of Kcv Conductance in Heterologous Expression Systems;41
4.2.6;6. Kcv is a K+ Selective Channel;41
4.2.7;7. Kcv has Some Voltage Dependency;41
4.2.8;8. Kcv has Distinct Sensitivity to K+ Channel Blockers;42
4.2.9;9. Ion Channel Function in Viral Replication;43
4.2.10;10. Kcv is Important for Viral Replication;44
4.2.11;11. Evolutionary Aspects of the kcv Gene;45
4.2.12;Acknowledgments;46
5;Part II Fusion Proteins;49
5.1;HIV gp41: A Viral Membrane Fusion Machine;50
5.1.1;1. Introduction;50
5.1.2;2. HIV Envelope Native Conformation;51
5.1.3;3. Receptor-Induced Conformational Changes;52
5.1.4;4. The Actual Membrane Fusion Step;54
5.1.5;5. HIV Entry Inhibitors;56
5.1.6;6. Final Remarks;58
5.1.7;Acknowledgment;58
5.1.8;References;59
5.2;Diversity of Coronavirus Spikes: Relationship to Pathogen Entry and Dissemination;63
5.2.1;1. Introduction;63
5.2.2;2. S Functions During Coronavirus Entry;65
5.2.3;3. S Functions During Dissemination of Coronavirus Infections;68
5.2.4;4. S Polymorphisms Affect Coronavirus Pathogenesis;69
5.2.5;5. Applications to the SARS Coronavirus;72
5.2.6;6. Relevance to Antiviral Drug Developments;73
5.3;Aspects of the Fusogenic Activity of Influenza Hemagglutinin Peptides by Molecular Dynamics Simulations;78
5.3.1;1. Introduction;78
5.3.2;2. Methods;80
5.3.3;3. Results;80
5.3.4;4. Conclusions;86
5.3.5;Acknowledgments;86
6;Part III Viral Ion Channels/ viroporins;89
6.1;Viral Proteins that Enhance Membrane Permeability;90
6.1.1;1. Introduction;90
6.1.2;2. Measuring Alterations in Membrane Permeability;91
6.1.3;3. Viral Proteins that Modify Permeability;94
6.1.4;4. Membrane Permeabilization and Drug Design;97
6.1.5;Acknowledgments;99
6.2;FTIR Studies of Viral Ion Channels;102
6.2.1;1. Introduction;102
6.2.2;2. SSID FTIR;103
6.2.3;3. Examples;107
6.2.4;4. Future Directions;109
6.2.5;Acknowledgment;110
6.2.6;References;111
6.3;The M2 Proteins of Influenza A and B Viruses are Single- Pass Proton Channels;112
6.3.1;1. Introduction;112
6.3.2;2. Intrinsic Activity of the A/M2 Protein of Influenza Virus;113
6.3.3;3. Mechanisms for Ion Selectivity and Activation of the A/ M2 Ion Channel;116
6.3.4;4. The BM2 Ion Channel of Influenza B Virus;118
6.3.5;5. Conclusion;120
6.3.6;Acknowledgments;120
6.4;Influenza A Virus M2 Protein: Proton Selectivity of the Ion Channel, Cytotoxicity, and a Hypothesis on Peripheral Raft Association and Virus Budding;123
6.4.1;1. Determination of Ion Selectivity and Unitary Conductance;124
6.4.2;2. Cytotoxicity of Heterologous M2 Expression;129
6.4.3;3. The M2 Protein Associates with Cholesterol;129
6.4.4;4. M2 as a Peripheral Raft Protein and a Model of its Role in Virus Budding;132
6.4.5;Acknowledgment;136
6.5;Computer Simulations of Proton Transport Through the M2 Channel of the Influenza A Virus;141
6.5.1;1. Introduction;141
6.5.2;2. Overview of Experimental Results for the M2 Channel;142
6.5.3;3. Molecular Dynamics Simulations of Proton Transport in the M2 Channel;144
6.5.4;4. Possible Closed and Open Conformations;146
6.5.5;5. A Revised Gating Mechanism and Future Work;152
6.5.6;Acknowledgments;152
6.5.7;References;152
6.6;Structure and Function of Vpu from HIV-1;156
6.6.1;1. Introduction;156
6.6.2;2. Structure Determination of Vpu;157
6.6.3;3. Correlation of Structure and Function of Vpu;162
6.6.4;4. Summary;167
6.6.5;Acknowledgments;168
6.7;Structure, Phosphorylation, and Biological Function of the HIV- 1 Specific Virus Protein U ( Vpu);173
6.7.1;1. Introduction;174
6.7.2;2. Structure and Biochemistry of Vpu;175
6.7.3;3. Biochemical Analysis of Vpu Phosphorylation;178
6.8;Solid-State NMR Investigations of Vpu Structural Domains in Oriented Phospholipid Bilayers: Interactions and Alignment;184
6.8.1;1. Introduction;184
6.8.2;2. Peptide Synthesis;186
6.8.3;3. Results and Discussion;188
6.8.4;Acknowledgments;192
6.9;Defining Drug Interactions with the Viral Membrane Protein Vpu from HIV- 1;194
6.9.1;1. Introduction;194
6.9.2;2. The Methods;196
6.9.3;3. Analysis of Drug–Protein Interactions of Vpu with a Potential Blocker;197
6.9.4;4. How Realistic is the Protein Model?;203
6.9.5;5. The Putative Binding Site;204
6.9.6;6. Water in the Pore;205
6.9.7;7. MD Simulations for Drug Screening?;206
6.9.8;8. Other Viral Ion Channels and Blockers;206
6.9.9;9. Speculation of Binding Sites in the Cytoplasmic Site;207
6.9.10;10. Conclusions;207
6.9.11;Acknowledgments;207
6.9.12;References;207
6.10;Virus Ion Channels Formed by Vpu of HIV- 1, the 6K Protein of Alphaviruses and NB of Influenza B Virus;213
6.10.1;1. Virus Ion Channels;213
6.10.2;2. Vpu of HIV-1;215
6.10.3;3. Alphavirus 6K Proteins;222
6.10.4;4. NB of Influenza B Virus;228
6.11;The Alphavirus 6K Protein;238
6.11.1;1. Introduction;238
6.11.2;2. Methods to Assess Whether 6K is a Membrane- Active Protein;239
6.11.3;3. Synthesis of 6K During Virus Infection;243
6.11.4;4. Cell Membrane Permeabilization by 6K;243
6.11.5;5. Function of 6K During the Alphavirus Life Cycle;245
6.11.6;6. A Model of 6K Function in Virion Budding;246
6.11.7;Acknowledgments;247
7;Part IV Membrane- Spanning/Membrane Associated;250
7.1;The Structure, Function, and Inhibition of Influenza Virus Neuraminidase;251
7.1.1;1. Introduction;251
7.1.2;2. Structure of Influenza Virus Neuraminidase;253
7.1.3;3. Function of Influenza Virus Neuraminidase;259
7.1.4;4. Inhibition of Influenza Virus Neuraminidase;263
7.1.5;5. Conclusions;269
7.1.6;Acknowledgments;269
7.2;Interaction of HIV-1 Nef with Human CD4 and Lck;272
7.2.1;1. Introduction;272
7.2.2;2. Interaction of Nef with Human CD4;273
7.2.3;3. Interaction of Nef with Human Lck;281
8;Index;290