4MHG

Crystal structure of ETV6 bound to a specific DNA sequence

Summary for 4MHG

• Entry DOI: 10.2210/pdb4mhg/pdb
• Related: 2LF7 2LF8
• Descriptor: Specific 14 bp DNA, Complementary Specific 14 bp DNA, Transcription factor ETV6, ... (4 entities in total)
• Functional Keywords: ets domain, transcription factor, transcription-dna complex, transcription/dna
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 3
• Total formula weight: 21011.94

Authors

Chan, A.C.,De, S.,Coyne III, H.J.,Okon, M.,Murphy, M.E.,Graves, B.J.,McIntosh, L.P. (deposition date: 2013-08-29, release date: 2014-01-08, Last modification date: 2024-02-28)

Primary citation

De, S.,Chan, A.C.,Coyne, H.J.,Bhachech, N.,Hermsdorf, U.,Okon, M.,Murphy, M.E.,Graves, B.J.,McIntosh, L.P.
Steric Mechanism of Auto-Inhibitory Regulation of Specific and Non-Specific DNA Binding by the ETS Transcriptional Repressor ETV6.
J.Mol.Biol., 426:1390-1406, 2014

PubMed Abstract: DNA binding by the ETS transcriptional repressor ETV6 (or TEL) is auto-inhibited ~50-fold due to an α-helix that sterically blocks its ETS domain binding interface. Using NMR spectroscopy, we demonstrate that this marginally stable helix is unfolded, and not displaced to a non-inhibitory position, when ETV6 is bound to DNA containing a consensus (5')GGAA(3') recognition site. Although significantly lower in affinity, binding to non-specific DNA is auto-inhibited ~5-fold and is also accompanied by helix unfolding. Based on NMR chemical shift perturbations, both specific and non-specific DNA are bound via the same canonical ETS domain interface. However, spectral perturbations are smaller for the non-specific complex, suggesting weaker and less well-defined interactions than in the specific complex. In parallel, the crystal structure of ETV6 bound to a specific DNA duplex was determined. The structure of this complex reveals that a non-conserved histidine residue in the ETS domain recognition helix helps establish the specificity of ETV6 for DNA-binding sites containing (5')GGAA(3')versus(5')GGAT(3'). These studies provide a unified steric mechanism for attenuating ETV6 binding to both specific and non-specific DNA and expand the repertoire of characterized auto-inhibitory strategies utilized to regulate ETS factors.

PubMed: 24333486
DOI: 10.1016/j.jmb.2013.11.031

Experimental method

X-RAY DIFFRACTION (2.199 Å)