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PDBsum entry 1s32
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Structural protein/DNA
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PDB id
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1s32
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Contents |
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98 a.a.
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81 a.a.
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107 a.a.
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101 a.a.
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88 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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Molecular recognition of the nucleosomal "supergroove".
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Authors
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R.S.Edayathumangalam,
P.Weyermann,
J.M.Gottesfeld,
P.B.Dervan,
K.Luger.
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Ref.
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Proc Natl Acad Sci U S A, 2004,
101,
6864-6869.
[DOI no: ]
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PubMed id
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Abstract
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Chromatin is the physiological substrate in all processes involving eukaryotic
DNA. By organizing 147 base pairs of DNA into two tight superhelical coils, the
nucleosome generates an architecture where DNA regions that are 80 base pairs
apart on linear DNA are brought into close proximity, resulting in the formation
of DNA "supergrooves." Here, we report the design of a hairpin
polyamide dimer that targets one such supergroove. The 2-A crystal structure of
the nucleosome-polyamide complex shows that the bivalent "clamp"
effectively crosslinks the two gyres of the DNA superhelix, improves positioning
of the DNA on the histone octamer, and stabilizes the nucleosome against
dissociation. Our findings identify nucleosomal supergrooves as platforms for
molecular recognition of condensed eukaryotic DNA. In vivo, supergrooves may
foster synergistic protein-protein interactions by bringing two regulatory
elements into juxtaposition. Because supergroove formation is independent of the
translational position of the DNA on the histone octamer, accurate nucleosome
positioning over regulatory elements is not required for supergroove
participation in eukaryotic gene regulation.
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Figure 1.
Fig. 1. Site-specific recognition of nucleosomal DNA by
clamp PAs. (A) NCP146 structure (PDB ID code 1AOI [PDB]
, ref. 2) viewed with the superhelical axis along the z axis.
The particle pseudo-two-fold dyad axis (  ) is shown for
orientation. DNA (blue and white) and associated histone
proteins (H2A, yellow; H2B, red; H3, blue; H4, green) are shown
in sphere or surface representation. (B) Supergrooves in NCP146.
Shown is a different view of NCP146 with the superhelical axis
along the y axis. Color scheme is the same as in A. One of the
DNA supergrooves is indicated by two asterisks. (C) Chemical
structures of clamp PAs, PW12 to -14. (D) Hydrogen bonding model
of PW12 to its target DNA site. Circles with dots represent lone
pairs of N3 of purines and O2 of pyrimidines. Circles containing
H represent the N2 hydrogen of guanine. Putative hydrogen bonds
are illustrated by dotted lines.
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Figure 3.
Fig. 3. Schematic illustration of the predicted effect of
PA clamps on nucleosome dissociation. In the absence of ligand
binding, nucleosome dissociation initiates with unraveling of
the DNA ends, followed by dissociation of the (H2A-H2B) dimers,
and finally by the dissociation of the (H3-H4)[2] tetramer.
Binding clamp to the nucleosomes leads to the formation of a
closed  80-bp DNA supercoil that
prevents further disassembly of the nucleosomes.
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