Macromolecular Protein Complexes III: Structure and Function 3030589706, 9783030589707

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

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