The Three Functional States of Proteins explores how structured proteins, intrinsically disordered proteins, and phase separated proteins contribute to the complexity of cellular life, and offers insights into their roles in both health and disease. It discusses the latest research findings and highlight groundbreaking discoveries and innovative methodologies used to study these protein states. Traditionally, the different states of proteins have been defined based on their structures and functions. However, it is becoming increasingly clear that these criteria alone may not be sufficient to capture the complex and multifaceted properties of these molecules. Definitions based on thermodynamics and kinetics are now recognized as potentially more appropriate for comprehensively understanding protein states. Emerging evidence indicates that under physiological conditions, a majority of proteins possess the capability to exist in and transition between the native, droplet, and amyloid states. These distinct states play crucial roles in various cellular functions, influenced significantly by their physicochemical and structural properties. The book also considers the interactions among these states and discusses how their internal organization as individual molecules, as well as their collective organization as molecular assemblies are stabilized. Furthermore, it examines the processes by which these states are formed and the cellular functions associated with each specific state.
1. 13.1 Introduction - p. 213 2. 13.2 Phases and phase transitions - p. 214 3. 13.3 Intramolecular phase transitions in disordered proteins induced by interactions with binding partners - p. 226 4. 13.4 Proteins that catalyze and inhibit phase transitions: ice nucleation and antinucleation - p. 230 5. 13.5 Protein amorphous aggregation, fibrillation, and crystallization as intermolecular phase transitions - p. 231 6. 13.6 Reincarnation of liquid–liquid and liquid–gel phase transitions: drivers of the biogenesis of membrane-less organelles and biomolecular condensates - p. 238 7. 13.7 Conclusions - p. 240 8. Acknowledgments - p. 241 9. Author Contributions - p. 241 10. Funding - p. 241 11. Conflict of Interest - p. 241 12. References - p. 241 13. Chapter 14 Targeting phase separated protein states for drug discovery - p. 255 14. Chapter 15 Protein hydrogels: structure, characteristics, and applications - p. 275 15. Chapter 16 Interactions among the three protein states - p. 297 16. Chapter 17 Frustration and fuzziness in the three functional states of proteins - p. 315 17. Chapter 18 Thermoresponsive intrinsically disordered protein polymers - p. 333 18. Chapter 19 The evolution and exploration of intrinsically disordered and phase-separated protein states - p. 353 19. Chapter 20 Computational modeling of intrinsically disordered and phase-separated protein states - p. 381 20. Chapter 21 Molecular dynamics simulations of intrinsically disordered proteins, fuzzy complexes, and phase-separated protein states - p. 399 21. Chapter 22 Biological complexity of the phase-separated protein states - p. 407 22. Chapter 23 Protein structure–function continuum - p. 423 23. Index - p. 443
The Three Functional States of Proteins explores how structured proteins, intrinsically disordered proteins, and phase separated proteins contribute to the complexity of cellular life, and offers insights into their roles in both health and disease. It discusses the latest research findings and highlight groundbreaking discoveries and innovative methodologies used to study these protein states. Traditionally, the different states of proteins have been defined based on their structures and functions. However, it is becoming increasingly clear that these criteria alone may not be sufficient to capture the complex and multifaceted properties of these molecules. Definitions based on thermodynamics and kinetics are now recognized as potentially more appropriate for comprehensively understanding protein states. Emerging evidence indicates that under physiological conditions, a majority of proteins possess the capability to exist in and transition between the native, droplet, and amyloid states. These distinct states play crucial roles in various cellular functions, influenced significantly by their physicochemical and structural properties. The book also considers the interactions among these states and discusses how their internal organization as individual molecules, as well as their collective organization as molecular assemblies are stabilized. Furthermore, it examines the processes by which these states are formed and the cellular functions associated with each specific state.
1. 13.1 Introduction - p. 213 2. 13.2 Phases and phase transitions - p. 214 3. 13.3 Intramolecular phase transitions in disordered proteins induced by interactions with binding partners - p. 226 4. 13.4 Proteins that catalyze and inhibit phase transitions: ice nucleation and antinucleation - p. 230 5. 13.5 Protein amorphous aggregation, fibrillation, and crystallization as intermolecular phase transitions - p. 231 6. 13.6 Reincarnation of liquid–liquid and liquid–gel phase transitions: drivers of the biogenesis of membrane-less organelles and biomolecular condensates - p. 238 7. 13.7 Conclusions - p. 240 8. Acknowledgments - p. 241 9. Author Contributions - p. 241 10. Funding - p. 241 11. Conflict of Interest - p. 241 12. References - p. 241 13. Chapter 14 Targeting phase separated protein states for drug discovery - p. 255 14. Chapter 15 Protein hydrogels: structure, characteristics, and applications - p. 275 15. Chapter 16 Interactions among the three protein states - p. 297 16. Chapter 17 Frustration and fuzziness in the three functional states of proteins - p. 315 17. Chapter 18 Thermoresponsive intrinsically disordered protein polymers - p. 333 18. Chapter 19 The evolution and exploration of intrinsically disordered and phase-separated protein states - p. 353 19. Chapter 20 Computational modeling of intrinsically disordered and phase-separated protein states - p. 381 20. Chapter 21 Molecular dynamics simulations of intrinsically disordered proteins, fuzzy complexes, and phase-separated protein states - p. 399 21. Chapter 22 Biological complexity of the phase-separated protein states - p. 407 22. Chapter 23 Protein structure–function continuum - p. 423 23. Index - p. 443
