Two distinct DNA sequences recognized by transcription factors represent enthalpy and entropy optima.
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Authors
Yin, Yimeng
Jolma, Arttu
Zhu, Fangjie
Popov, Alexander
Xu, You
Nilsson, Lennart
Publication Date
2018-04-11Journal Title
Elife
ISSN
2050-084X
Publisher
eLife Sciences Publications, Ltd
Volume
7
Language
eng
Type
Article
Physical Medium
Electronic
Metadata
Show full item recordCitation
Morgunova, E., Yin, Y., Das, P. K., Jolma, A., Zhu, F., Popov, A., Xu, Y., et al. (2018). Two distinct DNA sequences recognized by transcription factors represent enthalpy and entropy optima.. Elife, 7 https://doi.org/10.7554/eLife.32963
Abstract
Most transcription factors (TFs) can bind to a population of sequences closely related to a single optimal site. However, some TFs can bind to two distinct sequences that represent two local optima in the Gibbs free energy of binding (ΔG). To determine the molecular mechanism behind this effect, we solved the structures of human HOXB13 and CDX2 bound to their two optimal DNA sequences, CAATAAA and TCGTAAA. Thermodynamic analyses by isothermal titration calorimetry revealed that both sites were bound with similar ΔG. However, the interaction with the CAA sequence was driven by change in enthalpy (ΔH), whereas the TCG site was bound with similar affinity due to smaller loss of entropy (ΔS). This thermodynamic mechanism that leads to at least two local optima likely affects many macromolecular interactions, as ΔG depends on two partially independent variables ΔH and ΔS according to the central equation of thermodynamics, ΔG = ΔH - TΔS.
Keywords
DNA recognition, biochemistry, chemical biology, enthalpy, entropy, epistasis, human, molecular biophysics, structural biology, thermodynamics, transcription factors, CDX2 Transcription Factor, DNA, Entropy, Homeodomain Proteins, Humans, Models, Molecular, Nucleic Acid Conformation, Protein Binding, Protein Conformation, Substrate Specificity, Thermodynamics
Identifiers
External DOI: https://doi.org/10.7554/eLife.32963
This record's URL: https://www.repository.cam.ac.uk/handle/1810/283431
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