Structure and Function of Intrinsically Disordered Proteins

ISBN: 9781420078923 出版年：2009 页码：362 Tompa, Peter Fersht, Alan CRC Press

Principles of Protein Structure and Function Physical Forces That Shape Protein Structure Primary Structure: Amino Acid Sequence Protein-Coding Genes Post-Translational Modifications of Amino Acids Hierarchical Description of Structure Folding of a Protein Unfolding of a Protein: Lessons from Polymer Theory The Limits of Global Descriptions of the Unfolded State Databases of Proteins and Protein Structures DisProt: The Database of Disordered Proteins The Classical Structure-Function Paradigm A Brief History of Protein Disorder Can We Define Disorder? The History of Disorder So We Have Disordered Proteins Indirect Techniques for Recognizing and Characterizing Protein Disorder Resistance to Heat Resistance to Chemical Denaturation Unusual SDS-PAGE Mobility Enhanced Proteolytic Sensitivity Limited Proteolysis and Local Structure Differential Scanning Calorimetry Isothermal Titration Calorimetry Chemical Cross-Linking H/D Exchange Hydrodynamic Techniques Gel Filtration (Size-Exclusion) Chromatography Dynamic Light Scattering Analytical Ultracentrifugation Small-Angle X-Ray Scattering Pulsed-Field Gradient NMR Spectroscopic Techniques for Characterizing Disorder X-Ray Crystallography Fluorescence Spectroscopy Fourier-Transform Infrared Resonance Spectroscopy Circular Dichroism Raman Optical Activity Spectroscopy Electron Paramagnetic Resonance Spectroscopy Electron Microscopy Atomic Force Microscopy Nuclear Magnetic Resonance Basic Principles Global Characterization by NMR Sequence-Specific Structural Information Special Applications Proteomic Approaches for the Identification of IDPs Expectations and Limitations of Proteomic Studies 2DE-MS Identification of Proteins in Extracts Enriched for Disorder Native/Urea 2DE Provides Direct Information on Disorder IDPs under Conditions Approaching In Vivo Macromolecular Crowding in the Cell In Vitro Approaches to Mimicking Crowding Conditions The State of IDPs In Vivo Physiological Half-Life of IDPs: No Signs of Rapid Degradation Indirect Considerations Underscoring Disorder of IDPs In Vivo Prediction of Disorder General Points Propensity-Based Predictors Machine-Learning Algorithms Prediction Based on Interresidue Contacts Prediction of Short and Long Regions of Disorder Separately Combination of Predictors: Meta-Servers Prediction of Functional Motifs in IDPs Comparison of the Accuracy of Predictors: The CASP Experiment A Better Target Prioritization in Structural Genomics Structure of IDPs Primary Structure of Disordered Proteins Secondary Structure of Disordered Proteins Ambiguity in Structure Tertiary Structure: Global Features of IDP Structures Dynamics of IDP Structure: The Time-Course of Fluctuations within the Ensemble A Readout of Structure: The Hydrate Layer of IDPs Biological Processes Enriched in Disorder Biological Functions Enriched with Disorder Disorder in Transcription/Transcription Regulation Disorder in Signaling Proteins Nucleic Acid-Containing Organelles Disorder in RNA-Binding Proteins: Transcription and RNA Folding Cytoskeletal Proteins Disorder in Stress Proteins Disorder and Metal Binding Disorder and Enzyme Activity Is There a Link between the Pattern of Disorder and Function? Molecular Functions of Disordered Proteins Entropic Chain Functions Display Site Functions Chaperone Functions Effector Functions Scavenger Functions Assembler Functions Prion Functions Evolution and Prevalence of Disorder Phylogenetic Distribution of Disorder Fast Evolution of IDPs by Point Mutations Fast Evolution of IDPs by Repeat Expansion Fast Evolution and Functionality of Disordered Proteins Structural Variability and Evolvability of New Functions Extension of the Structure-Function Paradigm Functions That Stem Directly from the Disordered State Recognition Functions: Recognition by Short Motifs Disorder-to-Order Transition in Recognition: Mechanistic and Thermodynamic Aspects Recognition Functions: Uncoupling Specificity from Binding Strength Implications of Disorder for the Kinetics of Interactions Adaptability and Moonlighting Nested Interfaces Disorder in the Bound State: Fuzziness Processivity of Binding Sequence Independence in Recognition Ultrasensitivity of Recognition Signal Propagation in the Structural Ensemble of IDPs Disorder and Alternative Splicing Molecular Mimicry by a Disordered Region Entropy Transfer in Chaperone Action Structural Disorder and Disease Structural Disorder and Cancer Structural Disorder in Proteins Involved in Cardiovascular Diseases, Diabetes, and Autoimmune Diseases Structural Disorder and Neurodegenerative Diseases Systemic Amyloidoses Common Themes in Amyloid Formation Does Structural Disorder Pose a Danger? Disorder in Pathogenic Organisms Rational Drug Design Based on Protein Disorder References