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  Structural basis for ATP-dependent chromatin remodelling by the INO80 complex

Eustermann, S., Schall, K., Kostrewa, D., Lakomek, K., Strauss, M., Moldt, M., et al. (2018). Structural basis for ATP-dependent chromatin remodelling by the INO80 complex. Nature, 556(7701), 386-390. doi:10.1038/s41586-018-0029-y.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0001-DA81-7 Version Permalink: http://hdl.handle.net/21.11116/0000-0001-DA82-6
Genre: Journal Article

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 Creators:
Eustermann, Sebastian1, Author
Schall, Kevin1, Author
Kostrewa, Dirk1, Author
Lakomek, Kristina1, Author
Strauss, Mike2, Author              
Moldt, Manuela1, Author
Hopfner, Karl-Peter1, Author
Affiliations:
1external, ou_persistent22              
2Scientific Service Groups, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565170              

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Free keywords: EM STRUCTURE DETERMINATION; SWR-C; DNA; H2A.Z; VISUALIZATION; NUCLEOSOMES; MECHANISMS; PROTEINS; SYSTEM; SWITCHScience & Technology - Other Topics;
 Abstract: 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 remodellers(1-3) 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 DNA(5-8). 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 angstrom and with major parts at 3.7 angstrom. 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 A 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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Language(s): eng - English
 Dates: 2018
 Publication Status: Published in print
 Pages: 15
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: ISI: 000430285200053
DOI: 10.1038/s41586-018-0029-y
 Degree: -

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Title: Nature
  Abbreviation : Nature
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 556 (7701) Sequence Number: - Start / End Page: 386 - 390 Identifier: ISSN: 0028-0836
CoNE: https://pure.mpg.de/cone/journals/resource/954925427238