DNA Electric Charge Oscillations Govern Protein–DNA Recognition

Josef Štěpánek (1, 2, 3) , Vladimír Kopecký, Jr. (1) , Pierre-Yves Turpin (2) , Zhenlin Li (4, 5) , Bernard Alpert (3) , Christian Zentz (3)

1 UK - Univerzita Karlova [Praha, Česká republika] = Charles University [Prague, Czech Republic]
2 Laboratoire Jean PERRIN
3 ER12
4 CHU Tenon [AP-HP]
5 UR4

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.

Domains: Human health and pathology

Josef Štěpánek, Vladimír Kopecký, Jr., Pierre-Yves Turpin, Zhenlin Li, Bernard Alpert, et al.. DNA Electric Charge Oscillations Govern Protein–DNA Recognition. PLoS ONE, 2015, 10 (4), pp.e0124444. ⟨10.1371/journal.pone.0124444⟩. ⟨hal-01224151⟩