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Energetic basis of uncoupling folding from binding for an intrinsically disordered protein.

Drobnak I, De Jonge N, Haesaerts S, Vesnaver G, Loris R, Lah J
J Am Chem Soc 135 1288-94 (2013)
Cited: 25 times
EuropePMC logo PMID: 23289531

Abstract

Intrinsically disordered proteins (IDPs) are proteins that lack a unique three-dimensional structure in their native state. Many have, however, been found to fold into a defined structure when interacting with specific binding partners. The energetic implications of such behavior have been widely discussed, yet experimental thermodynamic data is scarce. We present here a thorough thermodynamic and structural study of the binding of an IDP (antitoxin CcdA) to its molecular target (gyrase poison CcdB). We show that the binding-coupled folding of CcdA is driven by a combination of specific intramolecular interactions that favor the final folded structure and a less specific set of intermolecular contacts that provide a desolvation entropy boost. The folded structure of the bound IDP appears to be defined largely by its own amino acid sequence, with the binding partner functioning more as a facilitator than a mold to conform to. On the other hand, specific intermolecular interactions do increase the binding affinity up to the picomolar range. Overall, this study shows how an IDP can achieve very strong and structurally well-defined binding and it provides significant insight into the molecular forces that enable such binding properties.

Reviews - 3tcj mentioned but not cited (2)

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  2. Wake me when it's over - Bacterial toxin-antitoxin proteins and induced dormancy. Coussens NP, Daines DA. Exp Biol Med (Maywood) 241 1332-1342 (2016)

Articles - 3tcj mentioned but not cited (1)

  1. Co-Evolution of Intrinsically Disordered Proteins with Folded Partners Witnessed by Evolutionary Couplings. Pancsa R, Zsolyomi F, Tompa P. Int J Mol Sci 19 E3315 (2018)


Reviews citing this publication (5)

  1. Intrinsically disordered proteins and intrinsically disordered protein regions. Oldfield CJ, Dunker AK. Annu Rev Biochem 83 553-584 (2014)
  2. Physicochemical properties of cells and their effects on intrinsically disordered proteins (IDPs). Theillet FX, Binolfi A, Frembgen-Kesner T, Hingorani K, Sarkar M, Kyne C, Li C, Crowley PB, Gierasch L, Pielak GJ, Elcock AH, Gershenson A, Selenko P. Chem Rev 114 6661-6714 (2014)
  3. Advantages of proteins being disordered. Liu Z, Huang Y. Protein Sci 23 539-550 (2014)
  4. Toxin-Antitoxin Modules Are Pliable Switches Activated by Multiple Protease Pathways. Muthuramalingam M, White JC, Bourne CR. Toxins (Basel) 8 E214 (2016)
  5. Digested disorder: Quarterly intrinsic disorder digest (January/February/March, 2013). Uversky VN. Intrinsically Disord Proteins 1 e25496 (2013)

Articles citing this publication (17)

  1. Disorder and residual helicity alter p53-Mdm2 binding affinity and signaling in cells. Borcherds W, Theillet FX, Katzer A, Finzel A, Mishall KM, Powell AT, Wu H, Manieri W, Dieterich C, Selenko P, Loewer A, Daughdrill GW. Nat Chem Biol 10 1000-1002 (2014)
  2. A general model for toxin-antitoxin module dynamics can explain persister cell formation in E. coli. Gelens L, Hill L, Vandervelde A, Danckaert J, Loris R. PLoS Comput Biol 9 e1003190 (2013)
  3. Ribosome-dependent Vibrio cholerae mRNAse HigB2 is regulated by a β-strand sliding mechanism. Hadži S, Garcia-Pino A, Haesaerts S, Jurenas D, Gerdes K, Lah J, Loris R. Nucleic Acids Res 45 4972-4983 (2017)
  4. A frustrated binding interface for intrinsically disordered proteins. Jemth P, Mu X, Engström Å, Dogan J. J Biol Chem 289 5528-5533 (2014)
  5. IMPIPS: the immune protection-inducing protein structure concept in the search for steric-electron and topochemical principles for complete fully-protective chemically synthesised vaccine development. Patarroyo ME, Bermúdez A, Alba MP, Vanegas M, Moreno-Vranich A, Poloche LA, Patarroyo MA. PLoS One 10 e0123249 (2015)
  6. The Thermodynamic Basis of the Fuzzy Interaction of an Intrinsically Disordered Protein. Hadži S, Mernik A, Podlipnik Č, Loris R, Lah J. Angew Chem Int Ed Engl 56 14494-14497 (2017)
  7. A dual role in regulation and toxicity for the disordered N-terminus of the toxin GraT. Talavera A, Tamman H, Ainelo A, Konijnenberg A, Hadži S, Sobott F, Garcia-Pino A, Hõrak R, Loris R. Nat Commun 10 972 (2019)
  8. The intrinsically disordered regions of the Drosophila melanogaster Hox protein ultrabithorax select interacting proteins based on partner topology. Hsiao HC, Gonzalez KL, Catanese DJ, Jordy KE, Matthews KS, Bondos SE. PLoS One 9 e108217 (2014)
  9. Molecular mechanism governing ratio-dependent transcription regulation in the ccdAB operon. Vandervelde A, Drobnak I, Hadži S, Sterckx YG, Welte T, De Greve H, Charlier D, Efremov R, Loris R, Lah J. Nucleic Acids Res 45 2937-2950 (2017)
  10. The sequence-ensemble relationship in fuzzy protein complexes. Hadži S, Loris R, Lah J. Proc Natl Acad Sci U S A 118 e2020562118 (2021)
  11. Generating intrinsically disordered protein conformational ensembles from a Markov chain. Cukier RI. J Chem Phys 148 105102 (2018)
  12. Ter-Seq: A high-throughput method to stabilize transient ternary complexes and measure associated kinetics. Chattopadhyay G, Ahmed S, Srilatha NS, Asok A, Varadarajan R. Protein Sci 32 e4514 (2023)
  13. The free energy folding penalty accompanying binding of intrinsically disordered α-helical motifs. Hadži S, Lah J. Protein Sci 31 e4370 (2022)
  14. Unraveling the Thermodynamics of Ultra-tight Binding of Intrinsically Disordered Proteins. Zavrtanik U, Hadži S, Lah J. Front Mol Biosci 8 726824 (2021)
  15. Conformational Ensembles Exhibit Extensive Molecular Recognition Features. Cukier RI. ACS Omega 3 9907-9920 (2018)
  16. Dynamics-Based Regulatory Switches of Type II Antitoxins: Insights into New Antimicrobial Discovery. Lee KY, Lee BJ. Antibiotics (Basel) 12 637 (2023)
  17. The Thermodynamic Fingerprints of Ultra-Tight Nanobody-Antigen Binding Probed via Two-Color Single-Molecule Coincidence Detection. Schedler B, Yukhnovets O, Lindner L, Meyer A, Fitter J. Int J Mol Sci 24 16379 (2023)


Related citations provided by authors (1)

  1. Purification and crystallization of Vibrio fischeri CcdB and its complexes with fragments of gyrase and CcdA.. De Jonge N, Buts L, Vangelooven J, Mine N, Van Melderen L, Wyns L, Loris R Acta Crystallogr Sect F Struct Biol Cryst Commun 63 356-60 (2007)

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