6FML

CryoEM Structure INO80core Nucleosome complex

Summary for 6FML

• Entry DOI: 10.2210/pdb6fml/pdb
• Related: 6FHS
• EMDB information: 4264 4277 4278 4280
• Descriptor: RuvB-like helicase, Histone H4, Histone H2A type 1, ... (14 entities in total)
• Functional Keywords: ino80, nucleosome, atp dependent chromatin remodeller, dna binding protein
• Biological source: Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719); More
• Total number of polymer chains: 20
• Total formula weight: 915378.06

Authors

Eustermann, S.,Schall, K.,Kostrewa, D.,Strauss, M.,Hopfner, K. (deposition date: 2018-01-31, release date: 2018-04-25, Last modification date: 2024-05-15)

Primary citation

Eustermann, S.,Schall, K.,Kostrewa, D.,Lakomek, K.,Strauss, M.,Moldt, M.,Hopfner, K.P.
Structural basis for ATP-dependent chromatin remodelling by the INO80 complex.
Nature, 556:386-390, 2018

PubMed 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 such as the 15-subunit INO80 complex . 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. 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 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.

PubMed: 29643509
DOI: 10.1038/s41586-018-0029-y

Experimental method

ELECTRON MICROSCOPY (4.34 Å)