PT  - JOURNAL ARTICLE
AU  - Ekaterina Morgunova
AU  - Yimeng Yin
AU  - Pratyush K. Das
AU  - Arttu Jolma
AU  - Alexander Popov
AU  - You Xu
AU  - Lennart Nilsson
AU  - Jussi Taipale
TI  - Two distinct DNA sequences recognized by transcription factors represent enthalpy and entropy optima
AID  - 10.1101/205906
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 205906
4099  - http://biorxiv.org/content/early/2017/11/07/205906.short
4100  - http://biorxiv.org/content/early/2017/11/07/205906.full
AB  - 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). The common presence of at least two local optima is general to all macromolecular interactions, as ΔG depends on two partially independent variables ΔH and ΔS according to the central equation of thermodynamics, ΔG = ΔH - TΔS.