Table of contents : Preface Contents 1 Structure, Dynamics and Function of the 26S Proteasome Introduction Overview of the Ubiquitin-Proteasome System Ubiquitylation 26S Proteasome Holoenzyme History of Proteasome Structure Determination X-Ray Crystallography of Proteasome Components Early Electron Microscopy Studies of Proteasome at Low Resolution High-Resolution Cryo-EM Studies of Substrate-Free Proteasome Visualizing Atomic-Level Dynamics of Functional Proteasome Structures and Dynamics of the Proteasome Molecular Architecture of the Proteasome Complex Dynamics of the Proteasome Summary of Proteasome Dynamics Life Cycle of the Proteasome Proteasome Biogenesis Proteasome Assembly Cellular Proteasome Regulation Proteasome Destruction Mechanism of Substrate Selection and Ubiquitin Recognition Degradation Signals Ubiquitin Recognition at the Proteasome Delivery of Substrates to the Proteasome Mechanism of Substrate Deubiquitylation Intrinsic Deubiquitinase RPN11 Mechanism of Substrate Deubiquitylation by RPN11 Deubiquitinase USP14 Deubiquitinase UCH37 Operating Principles of Proteasomal AAA-ATPase Motor Proteasomal AAA-ATPase Motor Conformational Dynamics of the AAA-ATPase Motor Principles of Coordinated ATP Hydrolysis in Functional Regulation Summary of Mechanism of the Proteasomal AAA-ATPase Motor Mechanism of Substrate Degradation in the CP Structural Mechanism of Substrate Proteolysis Proteolytic Products by the Proteasome Actions of the CP Inhibitors Proteasome in Health and Disease Cancer Aging Neurodegenerative Diseases Immune Diseases Cardiovascular Diseases Perspective References 2 Factor VIII and Factor V Membrane Bound Complexes Introduction Clotting Factors Cell Model of Coagulation The Tenase and Prothrombinase Complexes Factor V and Factor VIII Factor V Factor VIII The Factor VIII Structures FVIII Structure as Helically Organized on Lipid Nanotubes The Supertenase Complex Structural Basis of FVIII Activation-Future Perspectives Conclusions References 3 An Overview of Dps: Dual Acting Nanovehicles in Prokaryotes with DNA Binding and Ferroxidation Properties Introduction Discovery of DNA Binding Proteins Under Starvation (Dps) Iron Oxidation and Storage Fe(II) Binding (Phase 1) Fe(II) Oxidation (Phase 2) Nucleation and Growth of Mineral Core (Phase 3) DNA Protection by Direct and Indirect Modes Dps Across the Prokaryota N-end Rule Degradation Non-specific DNA Binding Property Studies on Dps Deletion Mutants Higher Order Dps-DNA Assemblies Visualised Through Atomic Force Microscopy DNA-Dps Biocrystals Modes of DNA Protection and Regulation Protecting DNA From Damage Nucleoid Condensation in Response to Stress Role in Transcription Regulation Ferroxidation Properties Iron Uptake and Release Conserved Ferroxidase Active Site Iron Gating Mechanisms Binding to Other Metals Evolutionary Link with Ferritins Applications in Biotechnology and Nanomedicine Engineering of Nanoscale Devices Nanoparticles in Biomedicine References 4 Structure and Function of the Separase-Securin Complex Introduction Domain Organization of the Cysteine Protease Separase Diverse Functions of Separase Regulation of Separase Separase-Related Diseases and Drug Development Structures of the Separase-Securin Complex Summary References 5 The DNA Replication Machine: Structure and Dynamic Function Introduction Evolution and Structure of the Core Replisome Components Helicase DNA Polymerase Primase Clamps and Clamp Loaders Organization of Replisomes Bacterial Replisome Eukaryotic Replisome Clamps Mediate Polymerase Recycling During Okazaki Fragment Synthesis Bacteria Eukaryotes Assembly and Escape of Replicative Helicases from the Origin Bacterial Helicase Eukaryotic Helicase Assembly of Bacterial and Eukaryotic Replisomes Bacterial Replisome Eukaryotic Replisome Summary and Future Outlook References 6 Recent Progress in Structural Studies on the GT-C Superfamily of Protein Glycosyltransferases Introduction The Prokaryotic Protein N-glycosyltransferases: PglB and AglB Eukaryotic Protein N-glycosyltransferase: The OST Complexes Eukaryotic Protein O-mannosyltransferases: Pmt1 and Pmt2 Summary References 7 How Structures of Complement Complexes Guide Therapeutic Design Complement Understanding MAC at the Molecular Level Molecular Assembly of MAC Interactions with the Membrane Structure of MAC Converting Soluble Proteins into a Transmembrane Pore Regulating MAC Targeting C5 Activation Blocking Pore Formation Scavenging By-Products Future of Structure-Based Complement Therapeutics References 8 Architecture and Assembly of the Bacterial Flagellar Motor Complex Introduction Axial Structure Rotor Stator Type III Protein Export Apparatus Conclusions References 9 Cellulosomes: Highly Efficient Cellulolytic Complexes The Cellulosome—Introduction Cellulosomal Components The Scaffoldin Cohesins and Dockerins Enzymes Carbohydrate Binding Modules Anchoring Modules The X-Module Cellulosome Diversity Quaternary Structure Regulation of Cellulosomal Components Applications for Cellulosomes Concluding Remarks References 10 Leucine Dehydrogenase: Structure and Thermostability Introduction Amino Acid Metabolizing Enzymes Leucine Dehydrogenase Structure of LDH from G. Stearothermophilus Thermostability of GstLDH NAD+ Recognition by Gst LDH Structural Comparisons with Other LDHs NAD+ Interaction with GstLDH Thermostabilization by NAD+ Binding Conclusions References 11 Structure, Function and Physiology of 5-Hydroxytryptamine Receptors Subtype 3 Introduction General Overview Expression and Physiological Role Basic Structural Topology Ion Permeation and Channel Gating Observed Properties of 5-HT3R Ion Conductance Mechanisms Underlying Ion Permeation Pore Blocking Antagonists Ligand Binding Description of the Ligand Binding Site and Orthosteric Ligands Mechanisms Underlying Ligand Binding Allosteric Coupling of Ligand Binding and Channel Gating Observed Properties of Allosteric Coupling Mechanisms Underlying Coupling Between Ligand Binding and Ion Permeation Allosteric Modulators Conclusions References 12 The SF3b Complex is an Integral Component of the Spliceosome and Targeted by Natural Product-Based Inhibitors Introduction Splicing Overview U2 snRNP and the SF3b Subcomplex SF3B1 Disease Mutations Splicing Modulators Summary References 13 Interaction Networks of Ribosomal Expansion Segments in Kinetoplastids Why Expansion Segments? Expansion Segments in Kinetoplastid Ribosomes Are Large but Structurally Organized Expansion Segments Form Kinetoplastid-Specific Interaction Networks Compensatory Interaction Networks Concluding Remarks References 14 Hepatitis B Core Protein Capsids Hepatitis B Core Protein a Component of the Hepatitis B Virus Structure of Hepatitis B Core Protein HBc Forms Dimeric Building Blocks Hbc Dimers Assemble into Icosahedral Capsids Important Sites of the Assembly Domain The Tips of the Spikes The Hydrophobic Pocket Inside the Spikes The Hydrophobic Pocket at the Inter Dimer Interface The C-Terminal Domain (CTD) Evolution of Capsids HBc Capsids as Tool in Biotechnology References 15 Fibrinogen and Fibrin Fibrinogen Structure Quaternary Structure of Fibrinogen Tertiary Structure of Fibrinogen Domain Structure of Fibrinogen The Coiled-Coil Connectors Carbohydrate Moiety Conversion of Fibrinogen to Fibrin Formation of Monomeric Fibrin and A:a Knob-Hole Interactions Formation of Fibrin Protofibrils Formation of Fibrin Fibers Additional Molecular Interactions During Fibrin Polymerization Formation of a Fibrin Network Mechanical Properties of Clots Significance of Clot Mechanical Properties Basis of Clot Mechanical Properties Viscoelastic Properties of Fibrin Non-linear Elasticity and High Extensibility of Fibrin Multiscale Fibrin Mechanics Molecular Structural Basis of Fibrin Mechanics Modeling Fibrin Mechanical Properties Clot Properties and Disease Fibrin Clot Properties and Pathological Intravascular Coagulation Fibrin Clot Properties and Bleeding Summary References 16 Structural Organization and Protein-Protein Interactions in Human Adenovirus Capsid Introduction Structures and Interactions of Major Capsid Proteins Hexon Penton Base (PB) Fiber and PB Interactions Structures and Interactions of Minor (Cement) Proteins Protein IX Protein VIII Protein IIIa Protein VI Concluding Remarks References 17 A Structural Perspective on Gene Repression by Polycomb Repressive Complex 2 Introduction Composition of Functional PRC2 The Core Complex The Holo Complexes: PRC2.1 and PRC2.2 Structure-Function Analysis of PRC2 Overall Structure of PRC2.2 Structure of the Catalytic Module Structure of the Accessory Subunit-Binding Module Concluding Remarks and Future Perspectives References 18 Assembly and Function of the Anthrax Toxin Protein Translocation Complex Introduction Anthrax Protective Antigen and Prepore Formation Prepore Structure Nature and Role of the Host Receptor, CMG2 Loading of the Toxic Enzymes and Insights into Prepore Assembly Structures of Toxin-Laden PA The Prepore-Pore Transition Protein Translocation Trigger for the Prepore to Pore Transition References