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

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cam.issuedOnline2018-04-11
dc.contributor.authorMorgunova, Ekaterina
dc.contributor.authorYin, Yimeng
dc.contributor.authorDas, Pratyush K
dc.contributor.authorJolma, Arttu
dc.contributor.authorZhu, Fangjie
dc.contributor.authorPopov, Alexander
dc.contributor.authorXu, You
dc.contributor.authorNilsson, Lennart
dc.contributor.authorTaipale, Jussi
dc.contributor.orcidMorgunova, Ekaterina [0000-0002-7754-9021]
dc.contributor.orcidDas, Pratyush K [0000-0003-2822-9619]
dc.contributor.orcidTaipale, Jussi [0000-0003-4204-0951]
dc.date.accessioned2018-10-10T05:18:59Z
dc.date.available2018-10-10T05:18:59Z
dc.date.issued2018-04-11
dc.description.abstractMost 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.
dc.format.mediumElectronic
dc.identifier.doi10.17863/CAM.30798
dc.identifier.eissn2050-084X
dc.identifier.issn2050-084X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/283431
dc.languageeng
dc.language.isoeng
dc.publishereLife Sciences Publications, Ltd
dc.publisher.urlhttp://dx.doi.org/10.7554/elife.32963
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectDNA recognition
dc.subjectbiochemistry
dc.subjectchemical biology
dc.subjectenthalpy
dc.subjectentropy
dc.subjectepistasis
dc.subjecthuman
dc.subjectmolecular biophysics
dc.subjectstructural biology
dc.subjectthermodynamics
dc.subjecttranscription factors
dc.subjectCDX2 Transcription Factor
dc.subjectDNA
dc.subjectEntropy
dc.subjectHomeodomain Proteins
dc.subjectHumans
dc.subjectModels, Molecular
dc.subjectNucleic Acid Conformation
dc.subjectProtein Binding
dc.subjectProtein Conformation
dc.subjectSubstrate Specificity
dc.subjectThermodynamics
dc.titleTwo distinct DNA sequences recognized by transcription factors represent enthalpy and entropy optima.
dc.typeArticle
dcterms.dateAccepted2018-02-12
prism.publicationDate2018
prism.publicationNameElife
prism.volume7
rioxxterms.licenseref.startdate2018-04-11
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.7554/eLife.32963

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