intrinsically disordered proteins


Summary: Functional proteins that do not have unique, stable, folded, three-dimensional native structures or that possess non-ordered regions under physiological conditions. They are characterized by extraordinary structural flexibility and plasticity, which enable them to adopt different conformations in response to different stimuli or different interactions.

Top Publications

  1. Cordeiro T, Chen P, De Biasio A, Sibille N, Blanco F, Hub J, et al. Disentangling polydispersity in the PCNA-p15PAF complex, a disordered, transient and multivalent macromolecular assembly. Nucleic Acids Res. 2017;45:1501-1515 pubmed publisher
    ..This strategy paves the way for deciphering the structural bases of flexible, transient and multivalent macromolecular assemblies involved in pivotal biological processes. ..
  2. Fox S, Kannan S. Probing the dynamics of disorder. Prog Biophys Mol Biol. 2017;128:57-62 pubmed publisher
    b>Intrinsically disordered proteins (IDPs) play an important role in many diseases. IDPs are a large and important class of proteins; estimated to represent a significant fraction of many genomes...
  3. Tompa P. Multisteric regulation by structural disorder in modular signaling proteins: an extension of the concept of allostery. Chem Rev. 2014;114:6715-32 pubmed publisher
  4. Ou L, Matthews M, Pang X, Zhou H. The dock-and-coalesce mechanism for the association of a WASP disordered region with the Cdc42 GTPase. FEBS J. 2017;284:3381-3391 pubmed publisher
    b>Intrinsically disordered proteins (IDPs) play key roles in signaling and regulation. Many IDPs undergo folding upon binding to their targets...
  5. Xue B, Blocquel D, Habchi J, Uversky A, Kurgan L, Uversky V, et al. Structural disorder in viral proteins. Chem Rev. 2014;114:6880-911 pubmed publisher
  6. Staby L, O Shea C, Willemoes M, Theisen F, Kragelund B, Skriver K. Eukaryotic transcription factors: paradigms of protein intrinsic disorder. Biochem J. 2017;474:2509-2532 pubmed publisher
  7. Ahrens J, Nunez Castilla J, Siltberg Liberles J. Evolution of intrinsic disorder in eukaryotic proteins. Cell Mol Life Sci. 2017;74:3163-3174 pubmed publisher
    ..We discuss the interplay between secondary structure and disorder on evolutionary time-scales, the importance of disorder for eukaryotic proteome expansion and functional divergence, and the evolutionary dynamics of disorder. ..
  8. Bonetti D, Troilo F, Toto A, Brunori M, Longhi S, Gianni S. Analyzing the Folding and Binding Steps of an Intrinsically Disordered Protein by Protein Engineering. Biochemistry. 2017;56:3780-3786 pubmed publisher
    b>Intrinsically disordered proteins (IDPs) are functionally active despite lacking a well-defined three-dimensional structure...
  9. Olsen J, Teilum K, Kragelund B. Behaviour of intrinsically disordered proteins in protein-protein complexes with an emphasis on fuzziness. Cell Mol Life Sci. 2017;74:3175-3183 pubmed publisher
    b>Intrinsically disordered proteins (IDPs) do not, by themselves, fold into a compact globular structure...

More Information


  1. Sharma R, Kumar S, Tsunoda T, Patil A, Sharma A. Predicting MoRFs in protein sequences using HMM profiles. BMC Bioinformatics. 2016;17:504 pubmed publisher
    b>Intrinsically Disordered Proteins (IDPs) lack an ordered three-dimensional structure and are enriched in various biological processes...
  2. Uversky V. Intrinsic disorder here, there, and everywhere, and nowhere to escape from it. Cell Mol Life Sci. 2017;74:3065-3067 pubmed publisher
    ..some of the new aspects of intrinsic disorder, outline some fascinating ideas related to the intrinsically disordered proteins, their structure, and functionality, and show challenges related to the analysis of proteins ..
  3. Gibbs E, Cook E, Showalter S. Application of NMR to studies of intrinsically disordered proteins. Arch Biochem Biophys. 2017;628:57-70 pubmed publisher
  4. Crabtree M, Borcherds W, Poosapati A, Shammas S, Daughdrill G, Clarke J. Conserved Helix-Flanking Prolines Modulate Intrinsically Disordered Protein:Target Affinity by Altering the Lifetime of the Bound Complex. Biochemistry. 2017;56:2379-2384 pubmed publisher
    ..Increasing the level of residual structure in intrinsically disordered proteins (IDPs), which are overrepresented in these cellular processes, has been shown previously to enhance ..
  5. Rusinga F, Weis D. Soft interactions and volume exclusion by polymeric crowders can stabilize or destabilize transient structure in disordered proteins depending on polymer concentration. Proteins. 2017;85:1468-1479 pubmed publisher
    The effects of macromolecular crowding on the transient structure of intrinsically disordered proteins is not well-understood. Crowding by biological molecules inside cells could modulate transient structure and alter IDP function...
  6. Malka Gibor E, Kornreich M, Laser Azogui A, Doron O, Zingerman Koladko I, Harapin J, et al. Phosphorylation-Induced Mechanical Regulation of Intrinsically Disordered Neurofilament Proteins. Biophys J. 2017;112:892-900 pubmed publisher
    ..Using a model that explains the attractive electrostatic interactions induced by enzymatically added charges, we demonstrate that phosphorylation regulation is far richer and versatile than previously considered. ..
  7. Currie S, Lau D, Doane J, Whitby F, Okon M, McIntosh L, et al. Structured and disordered regions cooperatively mediate DNA-binding autoinhibition of ETS factors ETV1, ETV4 and ETV5. Nucleic Acids Res. 2017;45:2223-2241 pubmed publisher
    ..These distinguishing inhibitory elements provide a platform through which cellular triggers, such as protein-protein interactions or post-translational modifications, may specifically regulate the function of these oncogenic proteins. ..
  8. Al Naqshabandi M, Weis D. Quantifying Protection in Disordered Proteins Using Millisecond Hydrogen Exchange-Mass Spectrometry and Peptic Reference Peptides. Biochemistry. 2017;56:4064-4072 pubmed publisher
    The extent and location of transient structure in intrinsically disordered proteins (IDPs) provide valuable insights into their conformational ensembles and can lead to a better understanding of coupled binding and folding...
  9. Uversky V, Dave V, Iakoucheva L, Malaney P, Metallo S, Pathak R, et al. Pathological unfoldomics of uncontrolled chaos: intrinsically disordered proteins and human diseases. Chem Rev. 2014;114:6844-79 pubmed publisher
  10. Loris R, Garcia Pino A. Disorder- and dynamics-based regulatory mechanisms in toxin-antitoxin modules. Chem Rev. 2014;114:6933-47 pubmed publisher
  11. Balakrishnan S, Sarma S. Engineering Aromatic-Aromatic Interactions To Nucleate Folding in Intrinsically Disordered Regions of Proteins. Biochemistry. 2017;56:4346-4359 pubmed publisher
    ..These studies provide insights into the aromatic interactions that drive disorder-to-order transitions in intrinsically disordered regions of proteins and will aid in de novo protein design beyond small peptide scaffolds...
  12. Jensen M, Zweckstetter M, Huang J, Blackledge M. Exploring free-energy landscapes of intrinsically disordered proteins at atomic resolution using NMR spectroscopy. Chem Rev. 2014;114:6632-60 pubmed publisher
  13. Kjaergaard M, Kragelund B. Functions of intrinsic disorder in transmembrane proteins. Cell Mol Life Sci. 2017;74:3205-3224 pubmed publisher
    ..We finish the review by discussing the future challenges facing the membrane protein community regarding protein disorder. ..
  14. Borkosky S, Camporeale G, Chemes L, Risso M, Noval M, Sánchez I, et al. Hidden Structural Codes in Protein Intrinsic Disorder. Biochemistry. 2017;56:5560-5569 pubmed publisher
    ..the major transforming oncoprotein of human papillomaviruses, is a paradigmatic example among the intrinsically disordered proteins. Analysis of a large number of sequences of the same viral protein allowed for the identification of ..
  15. Ghag G, Holler C, Taylor G, Kukar T, Uversky V, Rangachari V. Disulfide bonds and disorder in granulin-3: An unusual handshake between structural stability and plasticity. Protein Sci. 2017;26:1759-1772 pubmed publisher
    ..This unusual handshake between disulfide bonds and disorder within GRN-3 could suggest a unique adaptation of intrinsically disordered proteins towards structural stability.
  16. Meng F, Uversky V, Kurgan L. Comprehensive review of methods for prediction of intrinsic disorder and its molecular functions. Cell Mol Life Sci. 2017;74:3069-3090 pubmed publisher
    ..However, research into methods that predict many not yet addressed functions of intrinsic disorder remains an outstanding challenge. ..
  17. Lin Y, Qiu D, Chang W, Yeh Y, Jeng U, Liu F, et al. The intrinsically disordered N-terminal domain of galectin-3 dynamically mediates multisite self-association of the protein through fuzzy interactions. J Biol Chem. 2017;292:17845-17856 pubmed publisher
    ..These fuzzy interactions are characteristic of intrinsically disordered proteins to achieve liquid-liquid phase separation, and we demonstrated that galectin-3 can also undergo ..
  18. Liu C, Wang T, Bai Y, Wang J. Electrostatic forces govern the binding mechanism of intrinsically disordered histone chaperones. PLoS ONE. 2017;12:e0178405 pubmed publisher
    ..Z-H2B. Both the intra-chain and inter-chain electrostatic interactions have direct impacts on the native collapsed structure and binding mechanism. ..
  19. Peterson L, Roy A, Christoffer C, Terashi G, Kihara D. Modeling disordered protein interactions from biophysical principles. PLoS Comput Biol. 2017;13:e1005485 pubmed publisher
    ..Moreover, the new technique significantly expands the capability of protein structure modeling and provides crucial insights into the molecular mechanisms of disordered PPIs. ..
  20. Covarrubias A, Cuevas Velazquez C, Romero Pérez P, Rendón Luna D, Chater C. Structural disorder in plant proteins: where plasticity meets sessility. Cell Mol Life Sci. 2017;74:3119-3147 pubmed publisher
    ..In this review, we present information of those intrinsically disordered proteins (IDPs) from plants for which their high level of predicted structural disorder has been correlated ..
  21. Mallik S, Ray T, Kundu S. Transiently disordered tails accelerate folding of globular proteins. FEBS Lett. 2017;591:2180-2191 pubmed publisher
    ..These results allow us to infer probable molecular mechanisms behind the TstDREF-mediated regulation of folding kinetics that challenge protein biochemists to assess by direct experimental testing. ..
  22. Hyde E, Callow P, Rajasekar K, Timmins P, Patel T, Siligardi G, et al. Intrinsic disorder in the partitioning protein KorB persists after co-operative complex formation with operator DNA and KorA. Biochem J. 2017;474:3121-3135 pubmed publisher
    ..We propose that the positive co-operativity between KorB, KorA and DNA results from conformational restriction of KorB on binding each partner, while maintaining disorder. ..
  23. Huang F, Oldfield C, Xue B, Hsu W, Meng J, Liu X, et al. Improving protein order-disorder classification using charge-hydropathy plots. BMC Bioinformatics. 2014;15 Suppl 17:S4 pubmed publisher
    ..the best of the tested hydropathy scales for separating large collections structured proteins and intrinsically disordered proteins (IDPs) on the C-H plot...
  24. Huang Y, Gao M, Yang F, Zhang L, Su Z. Deciphering the promiscuous interactions between intrinsically disordered transactivation domains and the KIX domain. Proteins. 2017;85:2088-2095 pubmed publisher
    ..This study highlights the importance of long-range electrostatic interactions in molecular recognition process involving multi-motif intrinsically disordered proteins and promiscuous interactions.
  25. Nygaard M, Kragelund B, Papaleo E, Lindorff Larsen K. An Efficient Method for Estimating the Hydrodynamic Radius of Disordered Protein Conformations. Biophys J. 2017;113:550-557 pubmed publisher
    b>Intrinsically disordered proteins play important roles throughout biology, yet our understanding of the relationship between their sequences, structural properties, and functions remains incomplete...
  26. Longhi S, Bloyet L, Gianni S, Gerlier D. How order and disorder within paramyxoviral nucleoproteins and phosphoproteins orchestrate the molecular interplay of transcription and replication. Cell Mol Life Sci. 2017;74:3091-3118 pubmed publisher
    ..Finally, the relevance of N-P interactions as promising targets for innovative antiviral approaches is underscored, and the functional advantages of structural disorder for paramyxoviruses are pinpointed. ..
  27. Habchi J, Tompa P, Longhi S, Uversky V. Introducing protein intrinsic disorder. Chem Rev. 2014;114:6561-88 pubmed publisher
  28. Kyne C, Crowley P. Short Arginine Motifs Drive Protein Stickiness in the Escherichia coli Cytoplasm. Biochemistry. 2017;56:5026-5032 pubmed publisher
    ..coli cytoplasm and demonstrate the potential of such motifs to modify protein interactions in living cells. These interactions must be considered in the design of (in vivo) nanoscale assemblies that rely on arginine-rich sequences...
  29. Rajiv C, Jackson S, Cocklin S, Eisenmesser E, Davis T. The spliceosomal proteins PPIH and PRPF4 exhibit bi-partite binding. Biochem J. 2017;474:3689-3704 pubmed publisher
    ..A discussion of how this bipartite interaction between PPIH and PRPF4 may modulate spliceosomal function is included. ..
  30. Maritan M, Cozzi R, Lo Surdo P, Veggi D, Bottomley M, Malito E. Crystal structures of human Fabs targeting the Bexsero meningococcal vaccine antigen NHBA. Acta Crystallogr F Struct Biol Commun. 2017;73:305-314 pubmed publisher
    ..This study also provides indirect evidence for the intrinsically disordered nature of two N-terminal regions of NHBA...
  31. Brucale M, Schuler B, Samori B. Single-molecule studies of intrinsically disordered proteins. Chem Rev. 2014;114:3281-317 pubmed publisher
  32. Uversky V. Introduction to intrinsically disordered proteins (IDPs). Chem Rev. 2014;114:6557-60 pubmed publisher
  33. Niżyński B, Dzwolak W, Nieznanski K. Amyloidogenesis of Tau protein. Protein Sci. 2017;26:2126-2150 pubmed publisher
    ..Here, we review the current literature on Tau aggregation and discuss mechanisms of propagation of Tau amyloid in the light of the prion-like paradigm. ..
  34. Hibino E, Inoue R, Sugiyama M, Kuwahara J, Matsuzaki K, Hoshino M. Identification of heteromolecular binding sites in transcription factors Sp1 and TAF4 using high-resolution nuclear magnetic resonance spectroscopy. Protein Sci. 2017;26:2280-2290 pubmed publisher
    ..These results indicate a prominent and exceptional binding mode for intrinsically disordered proteins other than the well-accepted concept of "coupled folding and binding."
  35. Heller G, Aprile F, Vendruscolo M. Methods of probing the interactions between small molecules and disordered proteins. Cell Mol Life Sci. 2017;74:3225-3243 pubmed publisher
    ..In discussing these techniques, we also point out directions for future developments. ..
  36. Biehl R, Richter D. Slow internal protein dynamics in solution. J Phys Condens Matter. 2014;26:503103 pubmed
    ..Here we focus on these large-scale domain fluctuations and show how the structure and dynamics of proteins can be assessed by small-angle neutron scattering and NSE. ..
  37. Chavali S, Gunnarsson A, Babu M. Intrinsically Disordered Proteins Adaptively Reorganize Cellular Matter During Stress. Trends Biochem Sci. 2017;42:410-412 pubmed publisher
    b>Intrinsically disordered proteins (IDPs) can protect cells from diverse stresses by forming higher order assemblies such as reversible aggregates or granules. Recently, Boothby et al...
  38. Hausrath A, Kingston R. Conditionally disordered proteins: bringing the environment back into the fold. Cell Mol Life Sci. 2017;74:3149-3162 pubmed publisher
    ..We argue that the surprise results from the failure to consider the role of the environment in protein structure formation and that conditional disorder arises as a natural consequence of the marginal stability of the folded state. ..
  39. Ozdilek B, Thompson V, Ahmed N, White C, Batey R, Schwartz J. Intrinsically disordered RGG/RG domains mediate degenerate specificity in RNA binding. Nucleic Acids Res. 2017;45:7984-7996 pubmed publisher
    ..Analysis of RGG/RG domains from FUS, FMRP and hnRNPU against a spectrum of contrasting RNAs reveals that each display degenerate binding specificity, while still displaying different degrees of preference for RNA. ..
  40. Tunnicliffe R, Lockhart Cairns M, Levy C, Mould A, Jowitt T, Sito H, et al. The herpes viral transcription factor ICP4 forms a novel DNA recognition complex. Nucleic Acids Res. 2017;45:8064-8078 pubmed publisher
    ..Therefore in common with its eukaryotic host, the viral transcription factor ICP4 utilizes disordered regions to enhance the affinity and tune the specificity of DNA interactions in tandem with a globular domain. ..
  41. Jakob U, Kriwacki R, Uversky V. Conditionally and transiently disordered proteins: awakening cryptic disorder to regulate protein function. Chem Rev. 2014;114:6779-805 pubmed publisher
  42. Berlow R, Dyson H, Wright P. Hypersensitive termination of the hypoxic response by a disordered protein switch. Nature. 2017;543:447-451 pubmed publisher
    ..regulatory switch is entirely dependent on the unique flexibility and binding properties of these intrinsically disordered proteins and probably exemplifies a common strategy used by the cell to respond rapidly to environmental ..
  43. Pauwels K, Lebrun P, Tompa P. To be disordered or not to be disordered: is that still a question for proteins in the cell?. Cell Mol Life Sci. 2017;74:3185-3204 pubmed publisher
    ..These are called intrinsically disordered proteins (IDPs) or intrinsically disordered regions (IDRs)...
  44. Jones C, Njomen E, Sjögren B, Dexheimer T, Tepe J. Small Molecule Enhancement of 20S Proteasome Activity Targets Intrinsically Disordered Proteins. ACS Chem Biol. 2017;12:2240-2247 pubmed publisher
    The 20S proteasome is the main protease for the degradation of oxidatively damaged and intrinsically disordered proteins. When accumulation of disordered or oxidatively damaged proteins exceeds proper clearance in neurons, imbalanced ..
  45. Lindström I, Dogan J. Native Hydrophobic Binding Interactions at the Transition State for Association between the TAZ1 Domain of CBP and the Disordered TAD-STAT2 Are Not a Requirement. Biochemistry. 2017;56:4145-4153 pubmed publisher
    ..b>Intrinsically disordered proteins (IDPs) are common in protein-protein interactions and are involved in numerous cellular processes...
  46. Okazawa H. Ultra-Early Phase pathologies of Alzheimer's disease and other neurodegenerative diseases. Proc Jpn Acad Ser B Phys Biol Sci. 2017;93:361-377 pubmed publisher
    ..I introduce our recent efforts in this orientation that have reached to the stage of non-clinical proof of concept applicable to clinical trials...
  47. Miskei M, Gregus A, Sharma R, Duro N, Zsolyomi F, Fuxreiter M. Fuzziness enables context dependence of protein interactions. FEBS Lett. 2017;591:2682-2695 pubmed publisher
    ..We propose that all these context-dependent functional changes are intertwined with structural multiplicity or dynamic disorder in protein assemblies and can only be described by stochastic structure-function relationships. ..
  48. Zerfaß C, Buchko G, Shaw W, Hobe S, Paulsen H. Secondary structure and dynamics study of the intrinsically disordered silica-mineralizing peptide P5 S3 during silicic acid condensation and silica decondensation. Proteins. 2017;85:2111-2126 pubmed publisher
    ..Thus, with an associated increase in ?-helical character, P5 S3 influences both the condensation of silicic acid into silica and its decondensation back to silicic acid. ..
  49. Nussinov R, Jang H, Tsai C, Liao T, Li S, Fushman D, et al. Intrinsic protein disorder in oncogenic KRAS signaling. Cell Mol Life Sci. 2017;74:3245-3261 pubmed publisher
    ..We believe that a broad picture helps to grasp and formulate key mechanisms in Ras cancer biology and assists in therapeutic intervention. ..
  50. Yu J, Dou X, Sha Y, Wang C, Wang H, Chen Y, et al. DisBind: A database of classified functional binding sites in disordered and structured regions of intrinsically disordered proteins. BMC Bioinformatics. 2017;18:206 pubmed publisher ) is a collection of experimentally supported binding sites in intrinsically disordered proteins and proteins with both structured and disordered regions...
  51. van der Lee R, Buljan M, Lang B, Weatheritt R, Daughdrill G, Dunker A, et al. Classification of intrinsically disordered regions and proteins. Chem Rev. 2014;114:6589-631 pubmed publisher
  52. Kızılsavaş G, Ledolter K, Kurzbach D. Hydrophobic Collapse of the Intrinsically Disordered Transcription Factor Myc Associated Factor X. Biochemistry. 2017;56:5365-5372 pubmed publisher
    ..These extremely dense, hydrophobically collapsed globules might be of importance for interconversion between different conformations of intrinsically disordered proteins.
  53. Theillet F, Binolfi A, Frembgen Kesner T, Hingorani K, Sarkar M, Kyne C, et al. Physicochemical properties of cells and their effects on intrinsically disordered proteins (IDPs). Chem Rev. 2014;114:6661-714 pubmed publisher