DNA Electric Charge Oscillations Govern Protein-DNA Recognition.
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.
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.
Josef
J
Štěpánek
Institute of Physics, Faculty of Mathematics and Physics, Charles University in Prague, Prague, Czech Republic.
Vladimír
V
Kopecký
Laboratoire Jean Perrin, UPMC Université Paris 06, CNRS FRE 3231, Paris, France.
Pierre-Yves
PY
Turpin
UR4, UPMC Université Paris 06, Paris, France.
Zhenlin
Z
Li
ER12, UPMC Université Paris 06, Paris, France.
Bernard
B
Alpert
ER12, UPMC Université Paris 06, Paris, France.
Christian
C
Zentz
D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D006801:Humans; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D059372:Nucleotide Motifs; D009841:Oligonucleotides / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D027602:Serum Response Element / Q000235:genetics*; D026362:Serum Response Factor / Q000737:chemistry* / Q000235:genetics; D013059:Spectrum Analysis, Raman; D055672:Static Electricity; D013816:Thermodynamics; D014158:Transcription, Genetic
D009841:Oligonucleotides; D010710:Phosphates; D011994:Recombinant Proteins; C476858:SRF protein, human; D026362:Serum Response Factor; D004247:DNA