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DNA Electric Charge Oscillations Govern Protein-DNA Recognition.

Štěpánek J, Kopecký V, Turpin PY, Li Z, Alpert B, Zentz C - PLoS ONE (2015)

Bottom Line: Thus, sequence-specific recognition of the CArG box by core-SRF cannot be explained only in terms of the three-dimensional structure of the SRE.A particular dynamic pairing process discriminates between the wild type and mutated complexes.Specific oscillations of the phosphate charge network of the SRE govern the recognition between both partners rather than an intrinsic set of conformations of the SRE.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire Jean Perrin, UPMC Université Paris 06, CNRS FRE 3231, Paris, France; ER12, UPMC Université Paris 06, Paris, France; Institute of Physics, Faculty of Mathematics and Physics, Charles University in Prague, Prague, Czech Republic.

ABSTRACT
The transcriptional activity of the serum response factor (SRF) protein is triggered by its binding to a 10-base-pair DNA consensus sequence designated the CArG box, which is the core sequence of the serum response element (SRE). Sequence-specific recognition of the CArG box by a core domain of 100 amino acid residues of SRF (core-SRF) was asserted to depend almost exclusively on the intrinsic SRE conformation and on the degree of protein-induced SRE bending. Nevertheless, this paradigm was invalidated by a temperature-dependent Raman spectroscopy study of 20-mer oligonucleotides involved in bonding interactions with core-SRF that reproduced both wild type and mutated c-fos SREs. Indeed, the SRE moieties that are complexed with core-SRF exhibit permanent interconversion dynamics between bent and linear conformers. Thus, sequence-specific recognition of the CArG box by core-SRF cannot be explained only in terms of the three-dimensional structure of the SRE. A particular dynamic pairing process discriminates between the wild type and mutated complexes. Specific oscillations of the phosphate charge network of the SRE govern the recognition between both partners rather than an intrinsic set of conformations of the SRE.

No MeSH data available.


Temperature effect on free core-SRF.The blue curve represents the Raman spectrum of free core-SRF at 15°C. The red curve is the spectral difference between the spectrum of the free core-SRF at 15°C minus the spectrum at 5°C.
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pone.0124444.g002: Temperature effect on free core-SRF.The blue curve represents the Raman spectrum of free core-SRF at 15°C. The red curve is the spectral difference between the spectrum of the free core-SRF at 15°C minus the spectrum at 5°C.

Mentions: Fig 2 shows the temperature dependence of free core-SRF. The most important change consists of a wavenumber upshift from 1668 to 1675 cm–1 of the amide I band, suggesting a larger proportion of β-sheets when the temperature increases [24]. In addition, the band at 1453 cm–1, assignable to deformation modes of aliphatic side chains, exhibits variations in the hydrophobic packing [24, 25]. In the temperature difference spectra of the core-SRF moieties bound to SREs, the hydrophobic packings are stabilized compared to the free protein, as revealed by the lack of the band at 1453 cm–1 in Fig 1.


DNA Electric Charge Oscillations Govern Protein-DNA Recognition.

Štěpánek J, Kopecký V, Turpin PY, Li Z, Alpert B, Zentz C - PLoS ONE (2015)

Temperature effect on free core-SRF.The blue curve represents the Raman spectrum of free core-SRF at 15°C. The red curve is the spectral difference between the spectrum of the free core-SRF at 15°C minus the spectrum at 5°C.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414483&req=5

pone.0124444.g002: Temperature effect on free core-SRF.The blue curve represents the Raman spectrum of free core-SRF at 15°C. The red curve is the spectral difference between the spectrum of the free core-SRF at 15°C minus the spectrum at 5°C.
Mentions: Fig 2 shows the temperature dependence of free core-SRF. The most important change consists of a wavenumber upshift from 1668 to 1675 cm–1 of the amide I band, suggesting a larger proportion of β-sheets when the temperature increases [24]. In addition, the band at 1453 cm–1, assignable to deformation modes of aliphatic side chains, exhibits variations in the hydrophobic packing [24, 25]. In the temperature difference spectra of the core-SRF moieties bound to SREs, the hydrophobic packings are stabilized compared to the free protein, as revealed by the lack of the band at 1453 cm–1 in Fig 1.

Bottom Line: Thus, sequence-specific recognition of the CArG box by core-SRF cannot be explained only in terms of the three-dimensional structure of the SRE.A particular dynamic pairing process discriminates between the wild type and mutated complexes.Specific oscillations of the phosphate charge network of the SRE govern the recognition between both partners rather than an intrinsic set of conformations of the SRE.

View Article: PubMed Central - PubMed

Affiliation: Laboratoire Jean Perrin, UPMC Université Paris 06, CNRS FRE 3231, Paris, France; ER12, UPMC Université Paris 06, Paris, France; Institute of Physics, Faculty of Mathematics and Physics, Charles University in Prague, Prague, Czech Republic.

ABSTRACT
The transcriptional activity of the serum response factor (SRF) protein is triggered by its binding to a 10-base-pair DNA consensus sequence designated the CArG box, which is the core sequence of the serum response element (SRE). Sequence-specific recognition of the CArG box by a core domain of 100 amino acid residues of SRF (core-SRF) was asserted to depend almost exclusively on the intrinsic SRE conformation and on the degree of protein-induced SRE bending. Nevertheless, this paradigm was invalidated by a temperature-dependent Raman spectroscopy study of 20-mer oligonucleotides involved in bonding interactions with core-SRF that reproduced both wild type and mutated c-fos SREs. Indeed, the SRE moieties that are complexed with core-SRF exhibit permanent interconversion dynamics between bent and linear conformers. Thus, sequence-specific recognition of the CArG box by core-SRF cannot be explained only in terms of the three-dimensional structure of the SRE. A particular dynamic pairing process discriminates between the wild type and mutated complexes. Specific oscillations of the phosphate charge network of the SRE govern the recognition between both partners rather than an intrinsic set of conformations of the SRE.

No MeSH data available.