Structure and Function of Intrinsically Disordered Proteins
Structure and Function of Intrinsically Disordered Proteins
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DOI：
10.1201/9781420078930
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发表时间：
2009-11
期刊：
影响因子：
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通讯作者：
P. Tompa;A. Fersht
中科院分区：
文献类型：
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作者：
P. Tompa;A. Fersht
蛋白质结构和功能的原理形成蛋白质结构的物理力量初级结构：氨基酸序列蛋白质编码基因氨基酸翻译后修饰蛋白质的结构折叠的分层描述蛋白质的展开：从聚合物理论的教训蛋白质和蛋白质结构的未展开状态数据库的全局描述的局限性无序蛋白质数据库经典结构-功能范式蛋白质无序简史我们能定义无序吗？无序的历史使我们有了无序蛋白质识别和表征蛋白质无序的间接技术耐热性化学变性异常SDS-PAGE迁移率增强蛋白水解敏感性有限蛋白水解和局部结构差示扫描量热法等温滴定量热法化学交联H/D交换水动力学技术凝胶过滤（粒径排除）色谱法动态光散射分析超离心小角度x射线散射脉冲场梯度核磁共振光谱表征无序技术x射线晶体学荧光光谱傅立叶变换红外共振光谱学圆二色拉曼光谱学电子顺磁共振光谱学电子显微镜原子力显微镜核磁共振基本原理核磁共振序列特异性结构信息全局表征蛋白质组学方法在IDPs鉴定中的应用蛋白质组学研究的期望和局限性2DE- ms鉴定失调天然/尿素富集提取物中的蛋白质2DE提供了在接近体内细胞大分子拥挤条件下失调IDPs的直接信息体外模拟拥挤条件的方法IDPs的状态体内IDPs的生理半衰期没有快速退化的迹象间接考虑强调国内流离失所者的紊乱在体内的紊乱预测一般点基于倾向的预测器机器学习算法基于残差接触的预测分别预测短区和长区紊乱的组合预测器：元服务器预测国内流离失所者功能基序的准确性比较CASP实验IDP结构基因组学中更好的目标优先排序紊乱蛋白的一级结构紊乱蛋白的二级结构结构上的模糊性三级结构：IDP结构的全局特征IDP结构的动力学：集合内波动的时间过程A结构的读出IDPs生物过程的水合物层富集紊乱的生物功能富集紊乱的转录紊乱/信号蛋白的转录调控紊乱含核酸细胞器RNA结合蛋白的紊乱：应激中的转录和RNA折叠细胞骨架蛋白紊乱蛋白质紊乱和金属结合紊乱和酶活性紊乱模式和功能之间是否存在联系？无序蛋白的分子功能熵链功能显示位点功能伴侣功能效应者功能清道夫功能组装者功能朊病毒功能进化与紊乱的流行无序的系统发育分布IDPs的点突变快速进化IDPs的重复扩展快速进化无序蛋白的结构变异性与新功能的演化性结构-功能的延伸直接源于无序状态的范式函数识别功能：识别中短基序的无序到有序转换：机制和热力学方面的识别功能：结合强度的解耦特异性对相互作用动力学的无序影响适应性和束缚状态下的嵌套界面无序识别中结合序列独立的模糊性、灵敏性和选择性剪接的结构集合中识别信号传播的超灵敏性——在心血管疾病、糖尿病、糖尿病蛋白中伴蛋白作用结构紊乱、疾病结构紊乱和癌症结构紊乱的无序区域熵转移和自身免疫性疾病结构紊乱和神经退行性疾病全身性淀粉样病变淀粉样蛋白形成的共同主题结构紊乱构成危险吗？基于蛋白质紊乱文献的病原生物紊乱的合理药物设计
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