The structural study of peptides belonging to the terminal
domains of histone H1 can be considered as a step toward the
understanding of the function of H1 in chromatin. The conformational
properties of the peptide Ac-EPKRSVAFKKTKKEVKKVATPKK (CH-1),
which belongs to the C-terminal domain of histone H1°
(residues 99–121) and is adjacent to the central globular
domain of the protein, were examined by means of 1H-NMR
and circular dichroism. In aqueous solution, CH-1 behaved as a
mainly unstructured peptide, although turn-like conformations in
rapid equilibrium with the unfolded state could be present.
Addition of trifluoroethanol resulted in a substantial increase
of the helical content. The helical limits, as indicated by
(i, i + 3) nuclear Overhauser effect (NOE) cross
correlations and significant up-field conformational shifts of the
Cα protons, span from Pro100 to Val116, with Glu99
and Ala117 as N- and C-caps. A structure calculation performed on
the basis of distance constraints derived from NOE cross peaks in
90% trifluoroethanol confirmed the helical structure of this region.
The helical region has a marked amphipathic character, due to the
location of all positively charged residues on one face of the
helix and all the hydrophobic residues on the opposite face. The
peptide has a TPKK motif at the C-terminus, following the
α-helical region. The observed NOE connectivities suggest
that the TPKK sequence adopts a type (I) β-turn conformation,
a σ-turn conformation or a combination of both, in fast
equilibrium with unfolded states. Sequences of the kind (S/T)P(K/R)(K/R)
have been proposed as DNA binding motifs. The CH-1 peptide, thus,
combines a positively charged amphipathic helix and a turn as
potential DNA-binding motifs.