Structural highlights
Function[CDX2_HUMAN] Involved in the transcriptional regulation of multiple genes expressed in the intestinal epithelium. Important in broad range of functions from early differentiation to maintenance of the intestinal epithelial lining of both the small and large intestine. Publication Abstract from PubMedMost 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 (DeltaG). 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 DeltaG. However, the interaction with the CAA sequence was driven by change in enthalpy (DeltaH), whereas the TCG site was bound with similar affinity due to smaller loss of entropy (DeltaS). This thermodynamic mechanism that leads to at least two local optima likely affects many macromolecular interactions, as DeltaG depends on two partially independent variables DeltaH and DeltaS according to the central equation of thermodynamics, DeltaG = DeltaH - TDeltaS. Two distinct DNA sequences recognized by transcription factors represent enthalpy and entropy optima.,Morgunova E, Yin Y, Das PK, Jolma A, Zhu F, Popov A, Xu Y, Nilsson L, Taipale J Elife. 2018 Apr 11;7. pii: 32963. doi: 10.7554/eLife.32963. PMID:29638214[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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