2p81 › Citations

The helix-turn-helix motif as an ultrafast independently folding domain: the pathway of folding of Engrailed homeodomain.

Religa TL, Johnson CM, Vu DM, Brewer SH, Dyer RB, Fersht AR
Proc Natl Acad Sci U S A 104 9272-7 (2007)
Cited: 43 times
EuropePMC logo PMID: 17517666

Abstract

Helices 2 and 3 of Engrailed homeodomain (EnHD) form a helix-turn-helix (HTH) motif. This common motif is believed not to fold independently, which is the characteristic feature of a motif rather than a domain. But we found that the EnHD HTH motif is monomeric and folded in solution, having essentially the same structure as in full-length protein. It had a sigmoidal thermal denaturation transition. Both native backbone and local tertiary interactions were formed concurrently at 4 x 10(5) s(-1) at 25 degrees C, monitored by IR and fluorescence T-jump kinetics, respectively, the same rate constant as for the fast phase in the folding of EnHD. The HTH motif, thus, is an ultrafast-folding, natural protein domain. Its independent stability and appropriate folding kinetics account for the stepwise folding of EnHD, satisfy fully the criteria for an on-pathway intermediate, and explain the changes in mechanism of folding across the homeodomain family. Experiments on mutated and engineered fragments of the parent protein with different probes allowed the assignment of the observed kinetic phases to specific events to show that EnHD is not an example of one-state downhill folding.

Articles - 2p81 mentioned but not cited (2)

  1. The helix-turn-helix motif as an ultrafast independently folding domain: the pathway of folding of Engrailed homeodomain. Religa TL, Johnson CM, Vu DM, Brewer SH, Dyer RB, Fersht AR. Proc Natl Acad Sci U S A 104 9272-9277 (2007)
  2. Critical Features of Fragment Libraries for Protein Structure Prediction. Trevizani R, Custódio FL, Dos Santos KB, Dardenne LE. PLoS One 12 e0170131 (2017)


Reviews citing this publication (10)

  1. Combining experiment and simulation in protein folding: closing the gap for small model systems. Schaeffer RD, Fersht A, Daggett V. Curr Opin Struct Biol 18 4-9 (2008)
  2. The lifelong maintenance of mesencephalic dopaminergic neurons by Nurr1 and engrailed. Alavian KN, Jeddi S, Naghipour SI, Nabili P, Licznerski P, Tierney TS. J Biomed Sci 21 27 (2014)
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  5. Kinetic barriers and the role of topology in protein and RNA folding. Sosnick TR. Protein Sci 17 1308-1318 (2008)
  6. Protein folds and protein folding. Schaeffer RD, Daggett V. Protein Eng Des Sel 24 11-19 (2011)
  7. Proteins Recognizing DNA: Structural Uniqueness and Versatility of DNA-Binding Domains in Stem Cell Transcription Factors. Yesudhas D, Batool M, Anwar MA, Panneerselvam S, Choi S. Genes (Basel) 8 E192 (2017)
  8. Designed Multifunctional Peptides for Intracellular Targets. Juretić D. Antibiotics (Basel) 11 1196 (2022)
  9. Folding and stability of globular proteins and implications for function. Travaglini-Allocatelli C, Ivarsson Y, Jemth P, Gianni S. Curr Opin Struct Biol 19 3-7 (2009)
  10. Mechanisms of protein folding. Ivarsson Y, Travaglini-Allocatelli C, Brunori M, Gianni S. Eur Biophys J 37 721-728 (2008)

Articles citing this publication (31)

  1. A transient and low-populated protein-folding intermediate at atomic resolution. Korzhnev DM, Religa TL, Banachewicz W, Fersht AR, Kay LE. Science 329 1312-1316 (2010)
  2. A vocabulary of ancient peptides at the origin of folded proteins. Alva V, Söding J, Lupas AN. Elife 4 e09410 (2015)
  3. Different members of a simple three-helix bundle protein family have very different folding rate constants and fold by different mechanisms. Wensley BG, Gärtner M, Choo WX, Batey S, Clarke J. J Mol Biol 390 1074-1085 (2009)
  4. Downhill versus barrier-limited folding of BBL 2: mechanistic insights from kinetics of folding monitored by independent tryptophan probes. Neuweiler H, Sharpe TD, Johnson CM, Teufel DP, Ferguson N, Fersht AR. J Mol Biol 387 975-985 (2009)
  5. Kinetics of chain motions within a protein-folding intermediate. Neuweiler H, Banachewicz W, Fersht AR. Proc Natl Acad Sci U S A 107 22106-22110 (2010)
  6. Cold denaturation of a protein dimer monitored at atomic resolution. Jaremko M, Jaremko Ł, Kim HY, Cho MK, Schwieters CD, Giller K, Becker S, Zweckstetter M. Nat Chem Biol 9 264-270 (2013)
  7. Malleability of folding intermediates in the homeodomain superfamily. Banachewicz W, Religa TL, Schaeffer RD, Daggett V, Fersht AR. Proc Natl Acad Sci U S A 108 5596-5601 (2011)
  8. pi-Turns: types, systematics and the context of their occurrence in protein structures. Dasgupta B, Chakrabarti P. BMC Struct Biol 8 39 (2008)
  9. Experimental and Computational Analysis of Protein Stabilization by Gly-to-d-Ala Substitution: A Convolution of Native State and Unfolded State Effects. Zou J, Song B, Simmerling C, Raleigh D. J Am Chem Soc 138 15682-15689 (2016)
  10. Folding of the KIX domain: characterization of the equilibrium analog of a folding intermediate using 15N/13C relaxation dispersion and fast 1H/2H amide exchange NMR spectroscopy. Schanda P, Brutscher B, Konrat R, Tollinger M. J Mol Biol 380 726-741 (2008)
  11. Refolding the engrailed homeodomain: structural basis for the accumulation of a folding intermediate. McCully ME, Beck DA, Fersht AR, Daggett V. Biophys J 99 1628-1636 (2010)
  12. How general is the nucleation-condensation mechanism? Nölting B, Agard DA. Proteins 73 754-764 (2008)
  13. Roles of conformational disorder and downhill folding in modulating protein-DNA recognition. Chu X, Muñoz V. Phys Chem Chem Phys 19 28527-28539 (2017)
  14. Sequence, structure, and cooperativity in folding of elementary protein structural motifs. Lai JK, Kubelka GS, Kubelka J. Proc Natl Acad Sci U S A 112 9890-9895 (2015)
  15. Investigation of homeodomain membrane translocation properties: insights from the structure determination of engrailed-2 homeodomain in aqueous and membrane-mimetic environments. Carlier L, Balayssac S, Cantrelle FX, Khemtémourian L, Chassaing G, Joliot A, Lequin O. Biophys J 105 667-678 (2013)
  16. Protein folding: adding a nucleus to guide helix docking reduces landscape roughness. Wensley BG, Kwa LG, Shammas SL, Rogers JM, Clarke J. J Mol Biol 423 273-283 (2012)
  17. Resolution of Two Sub-Populations of Conformers and Their Individual Dynamics by Time Resolved Ensemble Level FRET Measurements. Rahamim G, Chemerovski-Glikman M, Rahimipour S, Amir D, Haas E. PLoS One 10 e0143732 (2015)
  18. Guanidine hydrochloride-induced unfolding of the three heme coordination states of the CO-sensing transcription factor, CooA. Lee AJ, Clark RW, Youn H, Ponter S, Burstyn JN. Biochemistry 48 6585-6597 (2009)
  19. Infrared study of the folding mechanism of a helical hairpin: porcine PYY. Waegele MM, Gai F. Biochemistry 49 7659-7664 (2010)
  20. APL: An angle probability list to improve knowledge-based metaheuristics for the three-dimensional protein structure prediction. Borguesan B, Barbachan e Silva M, Grisci B, Inostroza-Ponta M, Dorn M. Comput Biol Chem 59 Pt A 142-157 (2015)
  21. Deconvoluting Protein (Un)folding Structural Ensembles Using X-Ray Scattering, Nuclear Magnetic Resonance Spectroscopy and Molecular Dynamics Simulation. Nasedkin A, Marcellini M, Religa TL, Freund SM, Menzel A, Fersht AR, Jemth P, van der Spoel D, Davidsson J. PLoS One 10 e0125662 (2015)
  22. Folding of the Pit1 homeodomain near the speed limit. Banachewicz W, Johnson CM, Fersht AR. Proc Natl Acad Sci U S A 108 569-573 (2011)
  23. Quantitative Assessment of Chirality of Protein Secondary Structures and Phenylalanine Peptide Nanotubes. Sidorova A, Bystrov V, Lutsenko A, Shpigun D, Belova E, Likhachev I. Nanomaterials (Basel) 11 3299 (2021)
  24. The folding of a family of three-helix bundle proteins: spectrin R15 has a robust folding nucleus, unlike its homologous neighbours. Kwa LG, Wensley BG, Alexander CG, Browning SJ, Lichman BR, Clarke J. J Mol Biol 426 1600-1610 (2014)
  25. REMD and umbrella sampling simulations to probe the energy barrier of the folding pathways of engrailed homeodomain. Jani V, Sonavane UB, Joshi R. J Mol Model 20 2283 (2014)
  26. Nearly symmetrical proteins: folding pathways and transition states. Zamparo M, Pelizzola A. J Chem Phys 131 035101 (2009)
  27. Traversing the folding pathway of proteins using temperature-aided cascade molecular dynamics with conformation-dependent charges. Jani V, Sonavane U, Joshi R. Eur Biophys J 45 463-482 (2016)
  28. Structural and biophysical properties of h-FANCI ARM repeat protein. Siddiqui MQ, Choudhary RK, Thapa P, Kulkarni N, Rajpurohit YS, Misra HS, Gadewal N, Kumar S, Hasan SK, Varma AK. J Biomol Struct Dyn 35 3032-3042 (2017)
  29. Temperature-induced partially unfolded state of hUBF HMG Box-5: conformational and dynamic investigations of the Box-5 thermal intermediate ensemble. Liu Z, Zhang J, Wang X, Ding Y, Wu J, Shi Y. Proteins 77 432-447 (2009)
  30. The human peripheral subunit-binding domain folds rapidly while overcoming repulsive Coulomb forces. Arbely E, Neuweiler H, Sharpe TD, Johnson CM, Fersht AR. Protein Sci 19 1704-1713 (2010)
  31. Post-translational modifications of Drosophila melanogaster HOX protein, Sex combs reduced. Banerjee A, Percival-Smith A. PLoS One 15 e0227642 (2020)


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