Two distinct DNA sequences recognized by transcription factors represent enthalpy and entropy optima

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Morgunova , E , Yin , Y , Das , P K , Jolma , A , Zhu , F , Popov , A , Xu , Y , Nilsson , L & Taipale , J 2018 , ' Two distinct DNA sequences recognized by transcription factors represent enthalpy and entropy optima ' , eLife , vol. 7 , 32963 . https://doi.org/10.7554/eLife.32963

Title: Two distinct DNA sequences recognized by transcription factors represent enthalpy and entropy optima
Author: Morgunova, Ekaterina; Yin, Yimeng; Das, Pratyush K.; Jolma, Arttu; Zhu, Fangjie; Popov, Alexander; Xu, You; Nilsson, Lennart; Taipale, Jussi
Contributor: University of Helsinki, Research Programs Unit
University of Helsinki, Genome-Scale Biology (GSB) Research Program
Date: 2018-04-11
Language: eng
Number of pages: 21
Belongs to series: eLife
ISSN: 2050-084X
URI: http://hdl.handle.net/10138/234672
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 (Delta G). 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 Delta G. However, the interaction with the CAA sequence was driven by change in enthalpy (Delta H), whereas the TCG site was bound with similar affinity due to smaller loss of entropy (Delta S). This thermodynamic mechanism that leads to at least two local optima likely affects many macromolecular interactions, as Delta G depends on two partially independent variables Delta H and Delta S according to the central equation of thermodynamics, Delta G = Delta H - T Delta S.
Subject: PROSTATE-CANCER RISK
BINDING SPECIFICITIES
CRYSTAL-STRUCTURE
HIGH-RESOLUTION
NUCLEIC-ACIDS
SIMPLE-MODELS
FORCE-FIELD
COMPLEX
PROTEINS
OPERATOR
3111 Biomedicine
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