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TitleThe flexibility of a homeodomain transcription factor heterodimer and its allosteric regulation by DNA binding.
Journal, issue, pagesFEBS J, Vol. 283, Issue 16, Page 3134-3154, Year 2016
Publish dateJul 25, 2016
AuthorsLisa Mathiasen / Erica Valentini / Stephane Boivin / Angela Cattaneo / Francesco Blasi / Dmitri I Svergun / Chiara Bruckmann /
PubMed AbstractTranscription factors are known to modify the DNA that they bind. However, DNA can also serve as an allosteric ligand whose binding modifies the conformation of transcriptional regulators. Here, we ...Transcription factors are known to modify the DNA that they bind. However, DNA can also serve as an allosteric ligand whose binding modifies the conformation of transcriptional regulators. Here, we describe how heterodimer PBX1:PREP1, formed by proteins playing major roles in embryonic development and tumorigenesis, undergoes an allosteric transition upon DNA binding. We demonstrate through a number of biochemical and biophysical methods that PBX1:PREP1 exhibits a structural change upon DNA binding. Small-angle X-ray scattering (SAXS), circular dichroism (CD), isothermal titration calorimetry (ITC), and limited proteolysis demonstrate a different shape, α-helical content, thermodynamic behavior, and solution environment of the holo-complex (with DNA) compared to the apo-complex (without DNA). Given that PBX1 as such does not have a defined DNA selectivity, structural changes upon DNA binding become major factors in the function of the PBX1:PREP1 complex. The observed changes are mapped at both the amino- and carboxy-terminal regions of the two proteins thereby providing important insights to determine how PBX1:PREP1 dimer functions.
DATABASE: Small-angle scattering data are available in SASBDB under accession numbers SASDAP7, SASDAQ7, and SASDAR7.
External linksFEBS J / PubMed:27390177
MethodsSAS (X-ray synchrotron)
Structure data

SASDAP7:
PBX1-PREB1 complex (Pre-B-cell leukemia transcription factor 1, PBX1 + Homeobox protein PKNOX1, PREP1)
Method: SAXS/SANS

SASDAR7:
DNA 22mer
Method: SAXS/SANS

Source
  • Homo sapiens (human)

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