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Figure 1.
Figure 1: Overall structure and biochemical analysis of the
CIA-I–histone-H3–H4 complex. a, The overall structure
of the CIA-I–histone-H3–H4 complex. CIA-I and histones H3
and H4 are shown in red, blue, and green, respectively. An
orange triangle indicates the HIRA (histone regulatory homologue
A) binding site^28. The molecular graphics were prepared by
PyMOL^29. b, Possible modification sites (stick model in orange)
and the different residues of human histone H3.1 and H3.3 in the
CIA-I–histone-H3–H4 complex (sphere model in pink, only
exposed residues are displayed). c, The histone H3–H3'
interaction in the nucleosome core^21. d, CIA-I–histone H3
interaction in the CIA-I–histone-H3–H4 complex. e,
Carboxy-terminal residues (Thr 96–Tyr 98) of histone H4
(green) form a parallel  -sheet
with a -strand
from H2A (yellow) in the nucleosome core^21. f, The C-terminal
fragment of histone H4 undergoes a conformational change on the
CIA-I–histone-H3–H4 complex formation through rotations of
main-chain  angles
of Gly 94 and Arg 95 by 95° and 75°, respectively.
Histone H4s in the present structure and the nucleosome
core are shown in green and light green, respectively. This
conformational change and formation of a new anti-parallel -sheet
might facilitate the histone H3–H4 tetramer-disruption. The
large effect (tetramer disruption) originating from a small
interaction (formation of -sheet)
is similar to the essence of Japanese Judo (Yawara): 'softness
tames toughness (ju yoku go wo seisu)'. Following the spirit of
Judo, we designated the mechanism as the 'Yawara split'. It is
intriguing to note that most histone chaperones have a -rich
structure. g, Pull-down assay with GST-tagged human CIA-I(155)
or GST (control), showing the stoichiometric interaction between
CIA and the histone H3–H4 complex. h, Determination of the
molecular weight of human CIA, histone dimer, tetramer, and
complexes by the static light-scattering method. LS and RI
represent the intensity of static light scattering and the
refractive index, respectively.
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