نقش چپرون‌های مولکولی در تا شدن ساختاری، عملکردهای بیولوژیکی و تعاملات دارویی پروتئین‌های مشتری (مرزهای زیست‌شناسی ساختاری، جلد 1)

Annotation "The book provides an updated panorama of the functional relevance of molecular chaperones in the proper folding of client factors, protein-protein interactions, the regulation of key biological functions, the development of ligand-based structural complexes and the consequent pharmacological or biotechnological applications of these processes. The involvement of molecular chaperones in several processes ranging from regulation of transcription factors and protein-protein interactions in bacteria to proteostasis, signaling pathways and cancer are also addressed. The book is an essential consulting tool for researchers, working professionals in academia or industry, and students of all levels who wish to obtain the most relevant and updated information currently available about protein folding and chaperones." CONTENTS 6 PREFACE 10 List of Contributors 12 Regulatory Roles for Hsp70 in Cancer Incidence and Tumor Progression 14 Taka Eguchi1, Benjamin J. Lang1, Ayesha Murshid1, Thomas Prince2, Jianlin Gong3 and Stuart K Calderwood1,* 14 1. INTRODUCTION 14 2. HSP70 PROTEINS IN THE CYTOPLASM AND NUCLEUS 15 3. MUTATION AND OVEREXPRESSION OF HSP72 IN CANCER 20 4. HSP72 AND THE HALLMARKS OF CANCER 22 4A. HSP72 Suppresses Apoptotic Cell Death in Cancer 22 4B. HSP72 and Senescence 23 4C. HSP72 in Tumor Initiation and Metastasis 23 4D. HsSP72 in Sustained Angiogenesis 24 5. DRUGGING HSP70 IN CANCER: ISOFORMS AND DRUGGABLE DOMAINS 24 5A. Targeting the HSP70 Substrate-Binding Domain (SBD) 25 5B. Targeting the HSP70 Nucleotide-Binding Domain 26 5C. Perturbation of HSP70-Protein Interactions 27 CONCLUSIONS 28 CONSENT FOR PUBLICATION 28 CONFLICT OF INTEREST 28 ACKNOWLEDGEMENTS 28 REFERENCES 28 Use of Coarse-Grained and All-Atom Molecular Dynamics to Study Hsp70 and Hsp40 Chaperone Action 36 Ewa I. Gołaś1,2,¶, Magdalena A. Mozolewska1,2,¶, Paweł Krupa1,2, Cezary Czaplewski1, Harold A. Scheraga2 and Adam Liwo1,* 36 INTRODUCTION 36 METHODS 37 RESULTS 38 Mechanism of Chaperone Cycle 38 Modeling Iron-sulfur Cluster Biogenesis 45 Modeling the Structure of Isu1 from Yeast 46 Modeling the Structure of the Binary Isu1-Jac1 Complex and Assessing the Stability of its Interactions 48 Preliminary Molecular-modeling Study of the Structure of the Isu1-Jac1-Ssq1 Ternary Complex 51 CONCLUSIONS AND OUTLOOK 54 CONSENT FOR PUBLICATION 55 CONFLICT OF INTEREST 55 ACKNOWLEDGEMENTS 55 REFERENCES 56 Quaternary Structure of Chaperones from the Hsp70 System Determined by Small Angle X-Ray Scattering (SAXS) and Analytical Ultra-centrifugation 60 Júlio C. Borges1 and Carlos H.I. Ramos2,* 60 INTRODUCTION 60 Protein Folding and Molecular Chaperones 60 Small Angle X-ray Scattering (SAXS) 63 Analytical Ultracentrifugation 64 The Hsp70-folding System 66 Human Mitochondrial GrpE, Conformational Modification upon Hsp70 Binding 68 Eukaryotic Hsp40s Types I and II, on the Position of the J Domain 70 FINAL REMARKS 77 CONSENT FOR PUBLICATION 77 CONFLICT OF INTEREST 77 ACKNOWLEDGMENTS 77 REFERENCES 77 Structural Characteristics of the TPR Protein-Hsp90 Interaction: A New Target in Biotechnology 86 Ana Cauerhff1,* and Mario D. Galigniana1,2 86 INTRODUCTION 87 TPR PROTEIN CHARACTERISTICS 88 Definition and Prediction of the Sequence and Basic Structure of TPR Motifs 88 Three Dimensional Structure 91 Curvature and Shape of the TPR Domain 91 Examples of TPR Protein Structures 92 Ligand Binding 93 Folding and Stability of TPR Proteins 94 Oligomerization, Stability and Biological Functions 96 Novel TPR Protein Design 98 SEQUENCE, FUNCTION, AND BASIC STRUCTURE OF HSP90 PROTEINS: HSP90 ALPHA AND BETA 99 Introduction 99 Hsp90 Isoforms 101 Sequence and Basic Structure of Hsp90 Proteins: Hsp90 α and β 102 Difference in Structure of Hsp90 α−and β−isoforms 106 Conformational Changes in Hsp90 107 Sequence of Conformational Changes Induced by ATP Binding to Hsp90 110 HSP90-TPR PROTEIN INTERACTIONS 111 Introduction 111 Chaperone Cycle in SHRs 112 Hop/Sti1 113 Overall Structure 113 Hop-Hsp90 Interaction: Structural and Biophysical Aspects 115 CyP40, FKBP51 and FKBP52 119 Function 119 CyP40 Overall Structure 120 Cyp40-Hsp90 Interaction: Structural Studies 123 FKBP51: Overall Structure and Implications 124 FKBP-like Domains 125 TPR Domain 126 FKBP51-Hsp90 Interaction: Structural Studies 128 FKBP52 Structure 129 FKBP-like Domains 129 TPR Domain 132 Comparison Between FKBP51 and FKBP52 133 FKBP52-Hsp90 Complex 135 FKBP52-FK506 Complex 135 Binding Studies of Immunophilins 136 CyP40, FKBP51 and FKBP52 Interaction with Hsp90: Physico-chemical Binding Studies 137 Secondary Structure and Stability of CyP40, FKBP51 and FKBP52 138 Stability of the CyP40, FKBP51 and FKBP52 139 PP5 139 Introduction 139 PP5 Overall Structure 140 TPR Domain 141 Catalytic Phosphatase Domain 141 Relationship Between Phosphatase Activity and Hsp90 Binding 142 Structural Aspects of PP5-Hsp90 Interaction 143 PP5-Hsp90 Binding Studies 145 Structural Considerations 146 PP5 Folding Biophysical Studies 147 CHIP 148 Introduction 148 Structure 149 Hsp90 C-Terminal Binding to the CHIP TPR Domain 152 Folding and Degradation Balance Mechanism 153 TARGETING HSP90 INTERACTIONS FOR BIOTECHNOLOGICAL APPLICATIONS 155 Introduction 155 Hsp90 and Cancer 157 Inhibitors of the N-terminal Domain of Hsp90 158 Inhibitors of the C-terminal Domain of Hsp90 163 Inhibitors of the Hsp90-TPR Interactions 164 FINAL CONSIDERATIONS 168 CONSENT FOR PUBLICATION 169 CONFLICT OF INTEREST 169 ACKNOWLEDGEMENTS 169 REFERENCES 169 GroEL Chaperonin: Interaction with Polypeptides Lacking a Rigid Tertiary Structure 187 Victor V. Marchenkov, Natalia Yu Marchenko and Gennady V. Semisotnov* 187 INTRODUCTION 187 Driving Forces of GroEL Interaction with Substrate Polypeptides 188 Location of Substrate Polypeptides within a GroEL Particle and Stoichiometry of this Complex 190 The Role of Ligands in GroEL Functioning 191 Biotechnological Applications of GroEL Interaction with Substrate Polypeptides 194 CONCLUSION 195 CONSENT FOR PUBLICATION 195 CONFLICT OF INTEREST 195 ACKNOWLEDGEMENTS 195 REFERENCES 195 Mechanisms of Protein Folding by Type II Chaperonins 203 Rebecca L. Plimpton1, José M. Valpuesta2 and Barry M. Willardson1,* 203 INTRODUCTION 204 Molecular Chaperones and Proteostasis 204 THE CHAPERONINS 206 CCT STRUCTURE 208 General Features 208 Subunit Arrangement 209 SUBSTRATE RECOGNITION 210 Substrate Binding Sites on CCT 210 CCT Binding Sites on Substrates 213 MECHANISM OF FOLDING 214 CCT CO-CHAPERONES 217 Hsc70 217 PFD 217 PhLP1 218 Pdcd5 219 CONCLUDING REMARKS 219 CONSENT FOR PUBLICATION 220 CONFLICT OF INTEREST 220 ACKNOWLEDGEMENTS 220 REFERENCES 220 Mechanisms and Functions of the Cytosolic DNAJ-Hsp70 Chaperone System 227 Imad Baaklini and Jason C. Young* 227 INTRODUCTION 227 HSP70 228 Hsp70 Structure 229 ATPase Cycle 230 HSP40/DNAJ CO-CHAPERONES 231 Classification 231 Domains of DNAJs 232 J Domain 232 G/F-rich Linker 233 Substrate Binding and Cys(Zn) Regions 234 Quaternary Structure 235 NUCLEOTIDE EXCHANGE FACTORS (NEF) 236 CHAPERONE FUNCTION 238 FUNCTIONS IN CELLS AND TISSUES 242 Neurological Diseases 243 Cancer 245 Mitochondrial Import 246 Ion Channels 247 Androgen Receptor 248 Activation-Induced Cytidine Deaminase 249 Viruses 249 OUTLOOK 250 CONSENT FOR PUBLICATION 250 CONFLICT OF INTEREST 250 ACKNOWLEDGEMENTS 250 REFERENCES 251

The book provides an updated panorama of the functional relevance of molecular chaperones in the proper folding of client factors, protein-protein interactions, the regulation of key biological functions, the development of ligand-based structural complex