A new use for the 'wing' of the 'winged' helix-turn-helix motif in the
HSF−DNA cocrystal
Otis Littlefield1, 2
& Hillary C.M. Nelson3
1
Department of Molecular and Cell Biology, University
of California, Berkeley, California 94720-3206
, USA.
2
Present address: Department of Molecular Biochemistry
and Biophysics, Yale University, New Haven, Connecticut
06520, USA.
3
Johnson Research Foundation and the Department of Biochemistry
and Biophysics, University of Pennsylvania School of Medicine,
Philadelphia, Pennsylvania 19104-6089, USA
.
The 1.75 Å crystal structure of the Kluyveromyces lactis heat
shock transcription factor (HSF) DNA-binding domain (DBD) complexed with DNA
reveals a protein−DNA interface with few direct major groove contacts
and a number of phosphate backbone contacts that are primarily water-mediated
interactions. The DBD, a 'winged' helix-turn-helix protein, displays a novel
mode of binding in that the 'wing' does not contact DNA like all others of
that class. Instead, the monomeric DBD, which crystallized as a symmetric
dimer to a pair of nGAAn inverted repeats, uses the 'wing' to form part of
the protein-protein contacts. This dimer interface is likely important for
increasing the DNA-binding specificity and affinity of the trimeric form of
HSF, as well as for increasing cooperativity between adjacent trimers.
