Vol. 168, No. 1, 1990 April 16, 1990
BIOCHEMICAL
A DNA-BINDING Riitta-Maaria
Received
February
HOMRODOHAIN IN HISTONS Hl
Hannermaa
Unit, Research University
Collagen Biochemistry,
AND BIOPHYSICAL RESEARCH COMMUNICATIONS Pages 254-260
23,
and
Jouko
Oikarinen
Biocenter and Oulu, Rajaanintie Finland
of
Department 52A,
of Medical SF-90220 Oulu,
1990
The structure of the globular domain of chicken histone Hl was compared here with that of the DNA-binding homeodomain in the Drosophila Antp protein, and they were observed to display considerable similarity. Both of them consist of three or four a-helices separated by well-defined turns _ Charged residues in the aminoterminal end of a3 are therefore suggested to be responsible for sequence-specific recognition of DNA by the histone. In addition, a2 of Hl, with a short leucine zipper in it, may be capable of protein-protein interaction in a similar manner to the other homeodomains. Q1990 Academic Press, Inc.
Homeotic
genes,
requirement
for
the
adequate
criptional
regulators
function
has to date
mouse,
but
firmed
primarily been
which
they
recognition
of DNA and consists
most
cases
located
folds
into
(4,5). of
A
or four
end
action
in
the major
other
hand,
a2
specific The of
DNA
histones externally
H2A, (10).
0006-291X/90
$1.50
It
is
around H3
hinge is
of the
with into
nucleosomes that
region
0 1990 by Academic Press, Inc. of reproduction in any form reserved.
where to interact
254
while the
the
in the
aminointer-
(6).
On
be
the
capable
proteins
in which
consists
three
a number
specific to
of the
enter
in and
turns
a3,
Hl binds all
is
those
shown
DNA strands with
homeotic
well-defined
regulatory
structure
and H4 (8,9),
thought
other
con-
molecules
structure been
been
residues,
with for
and
sequence-specific
by a2 and
DNA secondary
packed
a core
formed
Their
of
the
by
trans-
development.
acid
of
for
has also
the
70 amino parts
crucial
Drosophila
number
for
some cases
interaction
H2B,
to the
complex
Copyright All rights
twined
a
a (l-3).
in
embryonal
in
responsible
HD has in
DNA in eukaryotes
nucleus
comparable is
is code
proteins
separated
being
groove
protein-protein are
of about
proteins
of the
the
responsible
a-helices
of a3 probably
in
control
structure
DNA-binding
eukaryotes,
(HD)
aminoterminal
helix-turn-helix
bacterial
terminal
in the
in
ubiquitous
may similarly
presumably
of which
in most detail
homeodomain
is
three
located
elucidated
of these
well-conserved
proteins,
expression
body development
the presence
in man, where
The
sequential
two
(7). turns
pairs
of
nucleosome
and leave
DNA strands
the it
is
Vol.
168,
No.
1, 1990
BIOCHEMICAL
Interaction
surrounded
by.
the
of the
bottom
experiments, Polypeptide helical
length
of
takes
a-helices
of nucleosomes
to be a crucial
step
differentiated is
cells, recently
chromatography
produced
in
E. coli
(unpublxshed
results).
Hl isolated
suggesting a determinant
contradictory
sequence-specific Primary,
manner secondary
compared
here
contain
an HD-like
for
with
sequence-specific
solenoid
of certain process
with
areas
those
of the
may be triggered
the
by Hl
rat
that groove
structures
of the DNA-binding presumably with
MATERIALS The computer programs described used for DNA and protein sequence Sequence Data Bank to search for Molecular Modeller Program from visualize 3D structures of various
HD,
(14),
We have
liver
by
DNA
protein motif
been confirmed the
results
DNA sequence
These
proposals
interaction
(18),
specific
(19).
a DNA minor
structure,
the
chromatin
(15,16).
from
PCA extraction
tertiary
a-
of
appears
has also
positioning
and
composed
recognition
of interaction
earlier
the
structures
repressor
of Hl with
to the
DNA
kind
of nucleosome
for and its
H1.03-1acZ fusion 5'-TTGGCAnnnTGCCAA-3'
interaction
35 a-
domain
in which
and a histone
by conventional
that
data,
DNA-binding
to the
This
of
mostly
of Hl is
Hl binds
(17)
on
(13).
as a eukaryotic
that
and
accounting
domain
by means of Hl isolated
affinity
ever,
and this
to act
an N tail
these
order
repression
it
(11).
comprise
(CRP),
structure to higher
in the
thought
demonstrated
using
protein
an a-turn-a
opposite by cross-linking
crystallographic on the
COMMUNICATIONS
just
to 120 residues
The globular
from
is
structure
of 70 residues,
(12).
AMP-receptor
the
110
superimposable
through
Aggregation in
domain
which
Hl subtypes
as deduced is
cyclic places
which
various
RESEARCH
be demonstrated
to seal
of approximately
globular
backbone
bacterial
serve
of 220 residues
three
carbon
H3,
can also
of
C tail
central
total
nucleosome,
chains a
BIOPHYSICAL
of Hl with
and may thus
residues,
AND
results
thus may be
are,
Hl interacts
how-
in a non-
(20,21). of the
Hl
and
Hl is
conferring
it
subtypes the
observed
are to
capability
DNA.
AND METHODS by Pustell and Kafatos (22-24) were analysis, and the GeneBank' Genetic the various sequences. The Desktop Oxford University Press was used to regions of the Hl globular domain.
RESULTS AND DISCUSSION The
primary
protein unit,
(1,5),
and secondary structures of an HD from the which is regarded as a model for this unique
were
compared
the
globular
domain
the
two
sequences
with
those
of Hl
of the histone displaying
The primary
(12,13).
may be aligned
12% identity
255
with
that
and 34% similarity
Antennapedia functional structure
of
of the
HD, the
when
Vol.
166, No. 1, 1990
helix 2
helix 1 globular
domain of
chicken Fig-l.
Alignment with that for amino alignment. Residues
H1.O1
of the of the acids
primary structure globular domain and are used, identical or similar
domain codes
helix 3
of w
of the Antennapedia histone Hl. Single introduced for
homeoletter optimal
to those in the homeodomain are hatched, the amino acids being grouped (V, I, M, L), (P, A, G, S, T), of the three a-helices CD, E, N, Q), (K, R, H) and (F, Y, W). Positions and the homeodomain secondary in H5, representing Hl here, structures are depicted.
amino
acids
primary similar
were
structure function
noted
that
domain avian
as generally
homologous
only
that
secondary
area
of
almost
H5 consists
tallographic between
a2
folds
between becomes
1).
in
two polypeptide
interaction
with of
the
domain
in a similar
It various
should HDs
be (1)
The degree
the
or four
a-helices
together
by al,
whole
the
chains
DNA then
of be
globular
being
noted are
that not
the
residues
256
in
the
two. the
assumed
the
Hl
to
turn globular
sites The
for
tertiary
Hl/H5
CRP DNA-binding
HD
The helices
putative
on
crys-
structures
of
the
lie
structure
above.
in the
the
from The model
structures
aligned,
an
a2 and a3
secondary
superimposed
conserved
globular
a-turn-a
as described
of the
The
by a well-defined
of the
be superimposed
to that
of
DNA recognition.
primary also
of that
1).
(21).
separated
aligned
are
HD may also manner
from
basis
as deduced
to CRP,
a-helices
HD are
on the H5 (Fig.
The similarity
when Antp
known
By analogy
or four
illustrative, and
principally
called
may be deduced
three
of H1.O1
structure
held
2).
a2 and a3 (Fig.
domain the
of three
(Fig.
and a3 into
comprises
1).
enough to substantiate although it should
however,
of Hl is
and are data
convincing
Hl variant
antiparallel
(Fig.
in Hl.
structure
erythrocyte-specific
domain
approved
homology is not of the two domains,
the
and
The
also
grouped
globular
domain. be
subtypes.
conserved
Hydropathy
in
Vol.
168,
No.
1, 1990
BIOCHEMICAL
AND
BIOPHYSICAL
RESEARCH
COMMUNICATIONS
DNA
ATP helix
a
I i9
P
Leu zipper -.Fig.2. Helices
A schematic
representation
of
the
histone
ii1
tertiary
structure.
are depicted by the cylinders, and the putative sites for sequence-specific interaction with DNA and recognition of ATP by the arrows. A short leucine zipper in a2 that may capable of protein-protein interaction
analysis
is
however,
similar
exception
charge
of a3 (Fig.
structures, but
of
similar
Residues
in The
chicken
H1.O1
the
distribution 3).
the
analysis
suggests with part
in recognition project
to the
thus
been
interactions
well-conserved
H1.01
globular
along
They may
the N-terminal
Hl to be involved groove.
that
as has already
experiments, capable
depicted.
revealed,
share order
also
their
to similar
by the
the
with
the higher
crystallographic
two domains
be suggested
may even be
bases
on the
in
bottom
Asn77 and Ser'l' residues in side
of the helix
facing
the
case of
of the
the
the
major
case of
DNA
groove
helix 2
15
helix 1
10
helix 3
n
0
10
20
30
40
50
60
70
80
of the homeodomain-like Fig.3. Hydropathy analysis. Hydropathy plot structure in Hl (thick line) and that of the Antennapedia homeodomain are depicted by horizontal (thin line). Positions of a-helices in Hl lines.
257
HD
molecules such as DNA.
other
DNA
fold
easily
of a3 may of
and Antp
a-helices,
confirmed that
domain
Vol.
168,
No.
1, 1990
BIOCHEMICAL
AND
BIOPHYSICAL
RESEARCH
-
H1.O1
LSLAALKKALAAG
0
---Ii-i+
COMMUNICATIONS
_
l
A A w
Fig.4 A leucine zipper in histone 131. Alignment of the Primary structure of a2 in the globular domain of chicken H1.O1 with the consensus for leucine zippers. The helical structure of H5 is shown below, and the helical wheel on the right, to demonstrate the projection of hydrophobic residues to one side of the helix.
when
a
model
computer of
using
H5
not
in 59
66
is
domain
of
to DNA. is
in
globular
domain
nucleotides
binding interesting When
the
angles
monomers
in and
solenoid primary A been
be
DNA-binding
identified kind
Hl
case
resides
leucine taken
N tails
and the
in
the
unit,
narrow C tail
called
minor
groove
may occur of HI/H5
in
a
DNA
the N-terminal results
most
aggregation. the of
Hl
nucleothe
two
downstream per
has very
in an A+T rich These
the
of a continuous
taking
and DNA.
in
recently
results).
latter
interaction
258
importance very
to successive
former
in
between
consideration,
formation
between
HDs.
hinge
nucleosome
the
DNA
sites
in Hl,
an SPKK-repeat,
a primary
globular with
of ATP stimulate
zipper
a2 in
Hl
such as protein be of
into
the
other
in the
and bound
through
is
the
of the
concentrations
may mediate
dimer
result
in histones,
of interaction
and H2B and the
the
the
both
with approximately six nucleosomes of repressed heterochromatin.
constituent novel
it
staggered
would
structure
that
that
on DNA (unpublished
of the
a2 and a3 are
through
an upstream this
exceptionally This
between
easily
may
dimer,
is
dimerized
motif
function
possibility
molecules somes
recognition
of the
suggest
we have demonstrated low
to zipper
even when
and may therefore
to Hl and that
of Hl to its
proteins
be
model,
respect leucine
substrates,
region
Actually,
bind
When thinking
This
and C tail,
DNA binding.
with
may
nucleotide-binding
nucleotide
(26).
side
a
3D structure
computer
of interacting
with
by
zipper
to the
in the
homology
of using
the
added
thus
capable
previously
from a leucine
other
results is
displays
capable
and G,-proteins
modulating that
These
constructed
and the
DNA,
with
an HD that
HI/H5
enzymes
kinases
with
as demonstrated
A region various
hand,
to the opposite
of interacting
Hl/H5
and proteins,
other
When a2 is
(25).
interact
bound
is
and coordinates
On the 4)
to
capable
molecule
Gly 69 to LYSS'
from
project
thought
obviously
the
shown).
a2 (Fig.
and
residues
region
energy-minimization
(data
identified Leu
of the
place
Hl 30
turn,
nm the
recently with
an
region ends
(27-29). of H2A
suggest,
there-
Vol.
168,
No.
fore,
1, 1990
that
action,
BIOCHEMICAL
the
C tail
in addition
action
of
together
the
It
model
gather
chromatosome.
some
occur.
may
serve
as
spacing into
the
of
nucleosomes
the
in
a dimer
but
as
for
the
above
no direct
In
contrast,
it
nucleosome
(32).
that homodimers elucidated in the recently fusion
inter-
rich
regions
the
core
DNA and proteins irregular
and tight
in
Hl
be responsible
nucleothus
constant of the
to
for
this seal
may
but
packaging of
HI-directed
hinge
serve
Hl
and thereby
of Hl with
aggregation
may
nucleosome of
DNA strands
in vivo
and inter-
DNA
homopolymers
the
aggregation
of
eukaryotic
repression
is
model
for
evidence generally There
the
HI function
exists
to date
believed are
that
that
some hints,
to
only
HI binds confirm
one HI
however,
to this
monomer
suggesting
of HI may be formed (17,33). It remains to be future in more detail how the higher order aggregates
of HI are
HI-1acZ -
HI-DNA
(14,31).
per
we have
A+T
of the
ordered in a2 may
fact.
dimers
COMMUNICATIONS
domain
C tails
of HI with
observed
exists
and
with the
generation
while
globular
of Hl to the
that
and consequent
assumed
DNA
binding
interactions
zipper
It
C tail
interaction
leucine
activity
is
the
HI/H5
In addition, forces
chromatin
in the
and leaving
(30),
through
be involved
entering
of nucleosomes
nucleosomes
in the
for
These
driving
RESEARCH
domain.
be envisaged
the
BIOPHYSICAL
of the
SPKK-repeats
may easily
to
globular
interaction
be responsible
region. the
of HI may also
to the
Sequence-specific
AND
formed.
introduced protein
In order various
produced
in
to study
deletions
the
interactions
and point
mutations
of HI, to the
E. coli.
REFERENCES
2. 3. 4. 5. 6. 7. 6.
9. 10. 11. 12. 13. 14. 15.
Scott, M.P., Tamkun, J.W., and Hartzell, III, G.W. (1989) Biochim. Biophys. Acta 969, 25-48. Wright, C.V.E., Cho, K.W.Y., Oliver, G., and Derobertis, E.M. (1989) TIES 14, 52-56. Cell 55, 537-540. Levine, M., and Hoey, T. (1988) Otting, G., Qian, Y.-Q., Miiller, M., Affolter, M., Gehring, W., and Wiithrich, K. (1988) EMBO J. 7, 4305-4309. Qian, Y.-Q., Billeter, M., Otting, G., Muller, M., Gehring, W.J., and Wuthrich, K. (1989) Cell 59, 573-580. Brennan, R.G., and Matthews, B.W. (1989) TIBS 14, 286-290. Stern, S., Tanaka, M., and Herr, W. (1989) Nature 341, 624-630. Smith, J., Finch, J.T., and Thomas, J.O. Klug, A., Rhodes, D., (1980) Nature 267, 509-516. Morse, R.H., and Simpson, R.T. (1988) Cell 54, 285-287. C. (1988) EMBO J. 7, 3685-3691. Staynov, Z., and Crane-Robinson, Nikolaev, L.G., and Severin, E.S. (1978) Glotov, B.O., Itkes, A.V., FEBS Lett. 91, 149-152. C. (1989) Nucl. Acids Res. 17, R311-R346. Wells, D., and McBride, Clore, G-M., Gronenborn, A.M., Nilges, M., Sukumaran, D.K., and Zarbock, J. (1987) EMBO J. 6, 1833-1842. Weintraub, H. (1985) Cell 42, 705-711. Wolffe, A.P. (1989) EMBO J. 8, 527-538. 259
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Sun,
J.-M.,
245,
68-11.
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Wiaderkiewicz,
Ristiniemi,
J.,
AND
II.,
BIOPHYSICAL
RESEARCH
and Ruiz-Carrillo,
and Oikarinen,
J.
(1988)
Biochemistry and Hager, G.L. C., and Ptitsyn,
27,
H.,
(1987)
Satchwell,
and Travers,
(1989)
J.
A. Biol.
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Science
(1989)
Chem. 264,
2164-
2114. 18. 19.
20.
Sevall, J.S. Richard-Foy, Crane-Robinson,
5038-5044. EMBO J. 6, 2321-2328. O.B. (1989) Protein Engineering
2,
511-582. 21.
Turnell, 232,
W.G.,
22. Pustell, J., 23. Pustell, J., 24. Pustell, J., 25. Landschulz, 240, 26.
27. 28. 29.
S.C.,
A.A.
(1988)
FEBS Lett.
263-268.
and Kafatos, F.C. (1982) and Kafatos, F.C. (1984) and kafatos, F.C. (1986) W.H., Johnson, P.F., and
Nucl. Acids Res. 10, 51-59. Nucl. Acids Res. 12, 643-655. Nucl. Acids Res. 14, 479-488. McKnight, S.L. (1988) Science
1759-1764.
(1988) Biochem. Biophys. Ristiniemi, J., and Oikarinen, J. Commun. 153, 783-791. Suzuki, M. (1989) EMBO J. 8, 797-804. Churchill, M.E.A., and Suzuki, M. (1989) EMBO J. 8, 4189-4195. Izaurralde, E., Kas, E., and Laemmli, U.K. (1989) J. Mol. Biol.
Res.
210,
573-585.
Rodriguez-Campos, A., Shimamura, A., and Worcel, A. (1989) J. Mol. Biol. 209, 135-150. 31. Shimamura, A., Sapp, M., Rodriguez-Campos, A., and Worcel, A. (1989) Mol. Cell. Biol. 9, 5573-5584. 32. Ring, D., and Cole, R.D. (1983) J. Biol. Chem. 258, 15361-15364. 33. Nilsson, P., Hallberg, B., Thornell, A., and Grundstrijm, T. (1989) Nucl. Acids Res. 17, 4061-4075. 30.
260
BIOCHEMICAL
A DNA-BINDING Riitta-Maaria
Received
February
HOMRODOHAIN IN HISTONS Hl
Hannermaa
Unit, Research University
Collagen Biochemistry,
AND BIOPHYSICAL RESEARCH COMMUNICATIONS Pages 254-260
23,
and
Jouko
Oikarinen
Biocenter and Oulu, Rajaanintie Finland
of
Department 52A,
of Medical SF-90220 Oulu,
1990
The structure of the globular domain of chicken histone Hl was compared here with that of the DNA-binding homeodomain in the Drosophila Antp protein, and they were observed to display considerable similarity. Both of them consist of three or four a-helices separated by well-defined turns _ Charged residues in the aminoterminal end of a3 are therefore suggested to be responsible for sequence-specific recognition of DNA by the histone. In addition, a2 of Hl, with a short leucine zipper in it, may be capable of protein-protein interaction in a similar manner to the other homeodomains. Q1990 Academic Press, Inc.
Homeotic
genes,
requirement
for
the
adequate
criptional
regulators
function
has to date
mouse,
but
firmed
primarily been
which
they
recognition
of DNA and consists
most
cases
located
folds
into
(4,5). of
A
or four
end
action
in
the major
other
hand,
a2
specific The of
DNA
histones externally
H2A, (10).
0006-291X/90
$1.50
It
is
around H3
hinge is
of the
with into
nucleosomes that
region
0 1990 by Academic Press, Inc. of reproduction in any form reserved.
where to interact
254
while the
the
in the
aminointer-
(6).
On
be
the
capable
proteins
in which
consists
three
a number
specific to
of the
enter
in and
turns
a3,
Hl binds all
is
those
shown
DNA strands with
homeotic
well-defined
regulatory
structure
and H4 (8,9),
thought
other
con-
molecules
structure been
been
residues,
with for
and
sequence-specific
by a2 and
DNA secondary
packed
a core
formed
Their
of
the
by
trans-
development.
acid
of
for
has also
the
70 amino parts
crucial
Drosophila
number
for
some cases
interaction
H2B,
to the
complex
Copyright All rights
twined
a
a (l-3).
in
embryonal
in
responsible
HD has in
DNA in eukaryotes
nucleus
comparable is
is code
proteins
separated
being
groove
protein-protein are
of about
proteins
of the
the
responsible
a-helices
of a3 probably
in
control
structure
DNA-binding
eukaryotes,
(HD)
aminoterminal
helix-turn-helix
bacterial
terminal
in the
in
ubiquitous
may similarly
presumably
of which
in most detail
homeodomain
is
three
located
elucidated
of these
well-conserved
proteins,
expression
body development
the presence
in man, where
The
sequential
two
(7). turns
pairs
of
nucleosome
and leave
DNA strands
the it
is
Vol.
168,
No.
1, 1990
BIOCHEMICAL
Interaction
surrounded
by.
the
of the
bottom
experiments, Polypeptide helical
length
of
takes
a-helices
of nucleosomes
to be a crucial
step
differentiated is
cells, recently
chromatography
produced
in
E. coli
(unpublxshed
results).
Hl isolated
suggesting a determinant
contradictory
sequence-specific Primary,
manner secondary
compared
here
contain
an HD-like
for
with
sequence-specific
solenoid
of certain process
with
areas
those
of the
may be triggered
the
by Hl
rat
that groove
structures
of the DNA-binding presumably with
MATERIALS The computer programs described used for DNA and protein sequence Sequence Data Bank to search for Molecular Modeller Program from visualize 3D structures of various
HD,
(14),
We have
liver
by
DNA
protein motif
been confirmed the
results
DNA sequence
These
proposals
interaction
(18),
specific
(19).
a DNA minor
structure,
the
chromatin
(15,16).
from
PCA extraction
tertiary
a-
of
appears
has also
positioning
and
composed
recognition
of interaction
earlier
the
structures
repressor
of Hl with
to the
DNA
kind
of nucleosome
for and its
H1.03-1acZ fusion 5'-TTGGCAnnnTGCCAA-3'
interaction
35 a-
domain
in which
and a histone
by conventional
that
data,
DNA-binding
to the
This
of
mostly
of Hl is
Hl binds
(17)
on
(13).
as a eukaryotic
that
and
accounting
domain
by means of Hl isolated
affinity
ever,
and this
to act
an N tail
these
order
repression
it
(11).
comprise
(CRP),
structure to higher
in the
thought
demonstrated
using
protein
an a-turn-a
opposite by cross-linking
crystallographic on the
COMMUNICATIONS
just
to 120 residues
The globular
from
is
structure
of 70 residues,
(12).
AMP-receptor
the
110
superimposable
through
Aggregation in
domain
which
Hl subtypes
as deduced is
cyclic places
which
various
RESEARCH
be demonstrated
to seal
of approximately
globular
backbone
bacterial
serve
of 220 residues
three
carbon
H3,
can also
of
C tail
central
total
nucleosome,
chains a
BIOPHYSICAL
of Hl with
and may thus
residues,
AND
results
thus may be
are,
Hl interacts
how-
in a non-
(20,21). of the
Hl
and
Hl is
conferring
it
subtypes the
observed
are to
capability
DNA.
AND METHODS by Pustell and Kafatos (22-24) were analysis, and the GeneBank' Genetic the various sequences. The Desktop Oxford University Press was used to regions of the Hl globular domain.
RESULTS AND DISCUSSION The
primary
protein unit,
(1,5),
and secondary structures of an HD from the which is regarded as a model for this unique
were
compared
the
globular
domain
the
two
sequences
with
those
of Hl
of the histone displaying
The primary
(12,13).
may be aligned
12% identity
255
with
that
and 34% similarity
Antennapedia functional structure
of
of the
HD, the
when
Vol.
166, No. 1, 1990
helix 2
helix 1 globular
domain of
chicken Fig-l.
Alignment with that for amino alignment. Residues
H1.O1
of the of the acids
primary structure globular domain and are used, identical or similar
domain codes
helix 3
of w
of the Antennapedia histone Hl. Single introduced for
homeoletter optimal
to those in the homeodomain are hatched, the amino acids being grouped (V, I, M, L), (P, A, G, S, T), of the three a-helices CD, E, N, Q), (K, R, H) and (F, Y, W). Positions and the homeodomain secondary in H5, representing Hl here, structures are depicted.
amino
acids
primary similar
were
structure function
noted
that
domain avian
as generally
homologous
only
that
secondary
area
of
almost
H5 consists
tallographic between
a2
folds
between becomes
1).
in
two polypeptide
interaction
with of
the
domain
in a similar
It various
should HDs
be (1)
The degree
the
or four
a-helices
together
by al,
whole
the
chains
DNA then
of be
globular
being
noted are
that not
the
residues
256
in
the
two. the
assumed
the
Hl
to
turn globular
sites The
for
tertiary
Hl/H5
CRP DNA-binding
HD
The helices
putative
on
crys-
structures
of
the
lie
structure
above.
in the
the
from The model
structures
aligned,
an
a2 and a3
secondary
superimposed
conserved
globular
a-turn-a
as described
of the
The
by a well-defined
of the
be superimposed
to that
of
DNA recognition.
primary also
of that
1).
(21).
separated
aligned
are
HD may also manner
from
basis
as deduced
to CRP,
a-helices
HD are
on the H5 (Fig.
The similarity
when Antp
known
By analogy
or four
illustrative, and
principally
called
may be deduced
three
of H1.O1
structure
held
2).
a2 and a3 (Fig.
domain the
of three
(Fig.
and a3 into
comprises
1).
enough to substantiate although it should
however,
of Hl is
and are data
convincing
Hl variant
antiparallel
(Fig.
in Hl.
structure
erythrocyte-specific
domain
approved
homology is not of the two domains,
the
and
The
also
grouped
globular
domain. be
subtypes.
conserved
Hydropathy
in
Vol.
168,
No.
1, 1990
BIOCHEMICAL
AND
BIOPHYSICAL
RESEARCH
COMMUNICATIONS
DNA
ATP helix
a
I i9
P
Leu zipper -.Fig.2. Helices
A schematic
representation
of
the
histone
ii1
tertiary
structure.
are depicted by the cylinders, and the putative sites for sequence-specific interaction with DNA and recognition of ATP by the arrows. A short leucine zipper in a2 that may capable of protein-protein interaction
analysis
is
however,
similar
exception
charge
of a3 (Fig.
structures, but
of
similar
Residues
in The
chicken
H1.O1
the
distribution 3).
the
analysis
suggests with part
in recognition project
to the
thus
been
interactions
well-conserved
H1.01
globular
along
They may
the N-terminal
Hl to be involved groove.
that
as has already
experiments, capable
depicted.
revealed,
share order
also
their
to similar
by the
the
with
the higher
crystallographic
two domains
be suggested
may even be
bases
on the
in
bottom
Asn77 and Ser'l' residues in side
of the helix
facing
the
case of
of the
the
the
major
case of
DNA
groove
helix 2
15
helix 1
10
helix 3
n
0
10
20
30
40
50
60
70
80
of the homeodomain-like Fig.3. Hydropathy analysis. Hydropathy plot structure in Hl (thick line) and that of the Antennapedia homeodomain are depicted by horizontal (thin line). Positions of a-helices in Hl lines.
257
HD
molecules such as DNA.
other
DNA
fold
easily
of a3 may of
and Antp
a-helices,
confirmed that
domain
Vol.
168,
No.
1, 1990
BIOCHEMICAL
AND
BIOPHYSICAL
RESEARCH
-
H1.O1
LSLAALKKALAAG
0
---Ii-i+
COMMUNICATIONS
_
l
A A w
Fig.4 A leucine zipper in histone 131. Alignment of the Primary structure of a2 in the globular domain of chicken H1.O1 with the consensus for leucine zippers. The helical structure of H5 is shown below, and the helical wheel on the right, to demonstrate the projection of hydrophobic residues to one side of the helix.
when
a
model
computer of
using
H5
not
in 59
66
is
domain
of
to DNA. is
in
globular
domain
nucleotides
binding interesting When
the
angles
monomers
in and
solenoid primary A been
be
DNA-binding
identified kind
Hl
case
resides
leucine taken
N tails
and the
in
the
unit,
narrow C tail
called
minor
groove
may occur of HI/H5
in
a
DNA
the N-terminal results
most
aggregation. the of
Hl
nucleothe
two
downstream per
has very
in an A+T rich These
the
of a continuous
taking
and DNA.
in
recently
results).
latter
interaction
258
importance very
to successive
former
in
between
consideration,
formation
between
HDs.
hinge
nucleosome
the
DNA
sites
in Hl,
an SPKK-repeat,
a primary
globular with
of ATP stimulate
zipper
a2 in
Hl
such as protein be of
into
the
other
in the
and bound
through
is
the
of the
concentrations
may mediate
dimer
result
in histones,
of interaction
and H2B and the
the
the
both
with approximately six nucleosomes of repressed heterochromatin.
constituent novel
it
staggered
would
structure
that
that
on DNA (unpublished
of the
a2 and a3 are
through
an upstream this
exceptionally This
between
easily
may
dimer,
is
dimerized
motif
function
possibility
molecules somes
recognition
of the
suggest
we have demonstrated low
to zipper
even when
and may therefore
to Hl and that
of Hl to its
proteins
be
model,
respect leucine
substrates,
region
Actually,
bind
When thinking
This
and C tail,
DNA binding.
with
may
nucleotide-binding
nucleotide
(26).
side
a
3D structure
computer
of interacting
with
by
zipper
to the
in the
homology
of using
the
added
thus
capable
previously
from a leucine
other
results is
displays
capable
and G,-proteins
modulating that
These
constructed
and the
DNA,
with
an HD that
HI/H5
enzymes
kinases
with
as demonstrated
A region various
hand,
to the opposite
of interacting
Hl/H5
and proteins,
other
When a2 is
(25).
interact
bound
is
and coordinates
On the 4)
to
capable
molecule
Gly 69 to LYSS'
from
project
thought
obviously
the
shown).
a2 (Fig.
and
residues
region
energy-minimization
(data
identified Leu
of the
place
Hl 30
turn,
nm the
recently with
an
region ends
(27-29). of H2A
suggest,
there-
Vol.
168,
No.
fore,
1, 1990
that
action,
BIOCHEMICAL
the
C tail
in addition
action
of
together
the
It
model
gather
chromatosome.
some
occur.
may
serve
as
spacing into
the
of
nucleosomes
the
in
a dimer
but
as
for
the
above
no direct
In
contrast,
it
nucleosome
(32).
that homodimers elucidated in the recently fusion
inter-
rich
regions
the
core
DNA and proteins irregular
and tight
in
Hl
be responsible
nucleothus
constant of the
to
for
this seal
may
but
packaging of
HI-directed
hinge
serve
Hl
and thereby
of Hl with
aggregation
may
nucleosome of
DNA strands
in vivo
and inter-
DNA
homopolymers
the
aggregation
of
eukaryotic
repression
is
model
for
evidence generally There
the
HI function
exists
to date
believed are
that
that
some hints,
to
only
HI binds confirm
one HI
however,
to this
monomer
suggesting
of HI may be formed (17,33). It remains to be future in more detail how the higher order aggregates
of HI are
HI-1acZ -
HI-DNA
(14,31).
per
we have
A+T
of the
ordered in a2 may
fact.
dimers
COMMUNICATIONS
domain
C tails
of HI with
observed
exists
and
with the
generation
while
globular
of Hl to the
that
and consequent
assumed
DNA
binding
interactions
zipper
It
C tail
interaction
leucine
activity
is
the
HI/H5
In addition, forces
chromatin
in the
and leaving
(30),
through
be involved
entering
of nucleosomes
nucleosomes
in the
for
These
driving
RESEARCH
domain.
be envisaged
the
BIOPHYSICAL
of the
SPKK-repeats
may easily
to
globular
interaction
be responsible
region. the
of HI may also
to the
Sequence-specific
AND
formed.
introduced protein
In order various
produced
in
to study
deletions
the
interactions
and point
mutations
of HI, to the
E. coli.
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