Abstract
Two DNA binding proteins, Cro and the amino-terminal domain of the
repressor of bacteriophage 434 (434 Cro and 434 repressor) that regulate
gene expression and contain a helix-turn-helix (HTH) motif responsible
for their site-specific DNA recognition adopt very similar three-dimensional
structures when compared to each other. To reveal structural differences
between these two similar proteins, their dynamic structures, as examined
by normal mode analysis, are compared in this paper. Two kinds of structural
data, one for the monomer and the other for a complex with DNA, for each
protein, are used in the analyses. From a comparison between the monomers
it is found that the interactions of Ala-24 in 434 Cro or Val-24 in 434
repressor, both located in the HTH motif, with residues 44, 47, 48, and
51 located in the domain facing the motif, and the interactions between
residues 17, 18, 28, and 32, located in the HTH motif, cause significant
differences in the correlative motions of these residues. From the comparison
between the monomer and the complex with DNA for each protein, it was found
that the first helix in the HTH motif is distorted in the complex form.
While the residues in the HTH motif in 434 Cro have relatively larger positive
correlation coefficients of motions with other residues within the HTH
motif, such correlations are not large in the HTH motif of 434 repressor.
It is suggestive to their specificity because the 434 repressor is less
specific than 434 Cro. Although a structural comparison of proteins has
been performed mainly from a static or geometrical point of view, this
study demonstrates that the comparison from a dynamic point of view, using
the normal mode analysis, is useful and convenient to explore a difference
that is difficult to find only from a geometrical point of view, especially
for proteins very similar in structure.