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PDBsum entry 1p3p
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Structural protein/DNA
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PDB id
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1p3p
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Contents |
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100 a.a.
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81 a.a.
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107 a.a.
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93 a.a.
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structures of histone sin mutant nucleosomes reveal altered protein-Dna interactions.
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Authors
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U.M.Muthurajan,
Y.Bao,
L.J.Forsberg,
R.S.Edayathumangalam,
P.N.Dyer,
C.L.White,
K.Luger.
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Ref.
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EMBO J, 2004,
23,
260-271.
[DOI no: ]
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PubMed id
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Abstract
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Here we describe 11 crystal structures of nucleosome core particles containing
individual point mutations in the structured regions of histones H3 and H4. The
mutated residues are located at the two protein-DNA interfaces flanking the
nucleosomal dyad. Five of the mutations partially restore the in vivo effects of
SWI/SNF inactivation in yeast. We find that even nonconservative mutations of
these residues (which exhibit a distinct phenotype in vivo) have only moderate
effects on global nucleosome structure. Rather, local protein-DNA interactions
are disrupted and weakened in a subtle and complex manner. The number of lost
protein-DNA interactions correlates directly with an increased propensity of the
histone octamer to reposition with respect to the DNA, and with an overall
destabilization of the nucleosome. Thus, the disruption of only two to six of
the approximately 120 direct histone-DNA interactions within the nucleosome has
a pronounced effect on nucleosome mobility and stability. This has implications
for our understanding of how these structures are made accessible to the
transcription and replication machinery in vivo.
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Figure 1.
Figure 1 Location and structural context of histone Sin mutants.
(A) Overview of the NCP structure, viewed down the superhelical
axis. Only half of the DNA and associated proteins are shown.
SHLs are indicated by italic numbers from 0.5 (flanking the
nucleosomal dyad) to 6.5 (at the entry and exit point of the
DNA). The locations of the H4 L1 loop and the H3 L2 loop are
indicated in green and blue, respectively. Histone H3 is colored
in blue, H4 in green, H2A in yellow, and H2B in red. The box
indicates the location of Sin mutants. The nucleosomal dyad is
indicated (  ).
(B) Close-up of the Sin region showing the five residues
affected by Sin mutations. Dotted lines represent hydrogen
bonds. (C) Location of H4 Val-43 in the hydrophobic core at the
underside of the L1L2 loop arrangement. The view is similar as
in (B), with a slight rotation around the y-axis.
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Figure 5.
Figure 5 Changed solvent structure in H3 Arg-116 mutants. (A)
The 'van der Waals cup' formed by H3 Met-120, Pro-121, and
Lys-122, holding the chloride ion. 2Fo-Fc electron density,
contoured at 1 sigma, is shown in gold. (B) The same region is
shown for H3 Arg-116-His (blue). Note the missing density for
the chloride ion. (C) In H3 Arg-116-Ala, minor density is
observed for the chloride ion, indicating only partial
occupancy. (D) Superposition of the three structures, viewed
from above with respect to the views shown in (A -C). Wild type
is shown in wheat, and mutants in blue. The chloride ion is
omitted for clarity.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2004,
23,
260-271)
copyright 2004.
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