The sequence-specific High Mobility Group 1 box of TCF-1 adopts a predominantly α-helical conformation in solution

Leo Van Houte, Annemiek Van Oers, Marc Van De Wetering, Dennis Dooijes, Rob Kaptein, Hans Clevers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Scopus)

Abstract

The High Mobility Group (HMG) 1 box is a protein motif that mediates DNA binding in a novel family of transcription-regulating proteins. Several members of this family, including the lymphoid-specific proteins TCF-1 and LEF-1 and the mammalian sex-determining factor SRY, carry a single HMG box with affinity for the minor groove of the heptamer motif AACAAAG or variations thereof. To initiate studies on the structural characteristics of the TCF-1 HMG box, we have expressed the 87-amino acid HMG box in milligram quantities in Escherichia coli and purified the soluble peptide to >95% homogeneity. The peptide bound DNA with the same specificity as the complete protein and was capable of inducing DNA bending. Circular dichroism (CD) analysis revealed the TCF-1 HMG box to adopt an approximately 60% α-helix/40% random coil conformation in solution. In the presence of an equimolar amount of double-stranded DNA containing the cognate motif, the CD spectrum changed significantly, implying the induction of a structural modification upon DNA/protein association.

Original languageEnglish
Pages (from-to)18083-18087
Number of pages5
JournalJournal of Biological Chemistry
Volume268
Issue number24
Publication statusPublished - 25 Aug 1993

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