The Structure of Sox17 Bound to DNA Reveals a Conserved Bending Topology but Selective Protein Interaction Platforms

Paaventhan Palasingam, Ralf Jauch, Calista Keow Leng Ng, Prasanna Kolatkar

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Sox17 regulates endodermal lineage commitment and is thought to function antagonistically to the pluripotency determinant Sox2. To investigate the biochemical basis for the distinct functions of Sox2 and Sox17, we solved the crystal structure of the high mobility group domain of Sox17 bound to a DNA element derived from the Lama1 enhancer using crystals diffracting to 2.7 Å resolution. Sox17 targets the minor groove and bends the DNA by approximately 80°. The DNA architecture closely resembles the one seen for Sox2/DNA structures, suggesting that the degree of bending is conserved between both proteins and nucleotide substitutions have only marginal effects on the bending topology. Accordingly, affinities of Sox2 and Sox17 for the Lama1 element were found to be identical. However, when the Oct1 contact interface of Sox2 is compared with the corresponding region of Sox17, a significantly altered charge distribution is observed, suggesting differential co-factor recruitment that may explain their biological distinctiveness.

Original languageEnglish
Pages (from-to)619-630
Number of pages12
JournalJournal of Molecular Biology
Volume388
Issue number3
DOIs
Publication statusPublished - 8 May 2009
Externally publishedYes

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DNA
Proteins
Nucleotides

Keywords

  • DNA bending
  • HMG domain
  • protein-DNA recognition
  • stem cells
  • transcription

ASJC Scopus subject areas

  • Molecular Biology

Cite this

The Structure of Sox17 Bound to DNA Reveals a Conserved Bending Topology but Selective Protein Interaction Platforms. / Palasingam, Paaventhan; Jauch, Ralf; Ng, Calista Keow Leng; Kolatkar, Prasanna.

In: Journal of Molecular Biology, Vol. 388, No. 3, 08.05.2009, p. 619-630.

Research output: Contribution to journalArticle

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