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PDBsum entry 3mgr
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Structural protein/DNA
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PDB id
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3mgr
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Contents |
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99 a.a.
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79 a.a.
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104 a.a.
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99 a.a.
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87 a.a.
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References listed in PDB file
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Key reference
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Title
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Perturbations in nucleosome structure from heavy metal association.
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Authors
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K.Mohideen,
R.Muhammad,
C.A.Davey.
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Ref.
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Nucleic Acids Res, 2010,
38,
6301-6311.
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PubMed id
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Abstract
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Heavy metals have the potential to engage in strong bonding interactions and can
thus function in essential as well as toxic or therapeutic capacities. We
conducted crystallographic analyses of heavy cation binding to the nucleosome
core particle and found that Co(2+) and Ni(2+) preferentially associate with the
DNA major groove, in a sequence- and conformation-dependent manner. Conversely,
Rb(+) and Cs(+) are found to bind only opportunistically to minor groove
elements of the DNA, in particular at narrow AT dinucleotide sites. Furthermore,
relative to Mn(2+) the aggressive coordination of Co(2+) and Ni(2+) to guanine
bases is observed to induce a shift in histone-DNA register around the
nucleosome center by stabilizing DNA stretching over one region accompanied by
expulsion of two bases at an opposing location. These 'softer' transition metals
also associate with multiple histone protein sites, including inter-nucleosomal
cross-linking, and display a proclivity for coordination to histidine. Sustained
binding and the ability to induce structural perturbations at specific locations
in the nucleosome may contribute to genetic and epigenetic mechanisms of
carcinogenesis mediated by Co(2+) and Ni(2+).
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