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PDBsum entry 6fhs
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DNA binding protein
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PDB id
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6fhs
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Contents |
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449 a.a.
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439 a.a.
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267 a.a.
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36 a.a.
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103 a.a.
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441 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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Structural basis for ATP-Dependent chromatin remodelling by the ino80 complex.
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Authors
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S.Eustermann,
K.Schall,
D.Kostrewa,
K.Lakomek,
M.Strauss,
M.Moldt,
K.P.Hopfner.
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Ref.
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Nature, 2018,
556,
386-390.
[DOI no: ]
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PubMed id
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Abstract
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In the eukaryotic nucleus, DNA is packaged in the form of nucleosomes, each of
which comprises about 147 base pairs of DNA wrapped around a histone protein
octamer. The position and histone composition of nucleosomes is governed by
ATP-dependent chromatin remodellers1-3 such as the 15-subunit INO80
complex 4 . INO80 regulates gene expression, DNA repair and
replication by sliding nucleosomes, the exchange of histone H2A.Z with H2A, and
the positioning of + 1 and -1 nucleosomes at promoter DNA5-8. The
structures and mechanisms of these remodelling reactions are currently unknown.
Here we report the cryo-electron microscopy structure of the evolutionarily
conserved core of the INO80 complex from the fungus Chaetomium thermophilum
bound to a nucleosome, at a global resolution of 4.3 Å and with major parts
at 3.7 Å. The INO80 core cradles one entire gyre of the nucleosome through
multivalent DNA and histone contacts. An Rvb1/Rvb2 AAA+ ATPase
heterohexamer is an assembly scaffold for the complex and acts as a 'stator' for
the motor and nucleosome-gripping subunits. The Swi2/Snf2 ATPase motor binds to
nucleosomal DNA at superhelical location -6, unwraps approximately 15 base
pairs, disrupts the H2A-DNA contacts and is poised to pump entry DNA into the
nucleosome. Arp5 and Ies6 bind superhelical locations -2 and -3 to act as a
counter grip for the motor, on the other side of the H2A-H2B dimer. The Arp5
insertion domain forms a grappler element that binds the nucleosome dyad,
connects the Arp5 actin-fold and entry DNA over a distance of about 90 Å and
packs against histone H2A-H2B near the 'acidic patch'. Our structure together
with biochemical data 8 suggests a unified mechanism for nucleosome
sliding and histone editing by INO80. The motor is part of a macromolecular
ratchet, persistently pumping entry DNA across the H2A-H2B dimer against the
Arp5 grip until a large nucleosome translocation step occurs. The transient
exposure of H2A-H2B by motor activity as well as differential recognition of
H2A.Z and H2A may regulate histone exchange.
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