title: Structure and subunit topology of the INO80 chromatin remodeler and its nucleosome complex.
abstract: INO80/SWR1 family chromatin remodelers are complexes composed of >15 subunits and molecular masses exceeding 1 MDa. Their important role in transcription and genome maintenance is exchanging the histone variants H2A and H2A.Z. We report the architecture of S. cerevisiae INO80 using an integrative approach of electron microscopy, crosslinking and mass spectrometry. INO80 has an embryo-shaped head-neck-body-foot architecture and shows dynamic open and closed conformations. We can assign an Rvb1/Rvb2 heterododecamer to the head in close contact with the Ino80 Snf2 domain, Ies2, and the Arp5 module at the neck. The high-affinity nucleosome-binding Nhp10 module localizes to the body, whereas the module that contains actin, Arp4, and Arp8 maps to the foot. Structural and biochemical analyses indicate that the nucleosome is bound at the concave surface near the neck, flanked by the Rvb1/2 and Arp8 modules. Our analysis establishes a structural and functional framework for this family of large remodelers.
authors.affiliation: Department of Biochemistry, Ludwig-Maximilian University, 81377 Munich, Germany; Gene Center, Ludwig-Maximilian University, 81377 Munich, Germany.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Tosi
authors.forename: Caroline
authors.initials: C
authors.lastname: Haas
authors.forename: Franz
authors.initials: F
authors.lastname: Herzog
authors.forename: Andrea
authors.initials: A
authors.lastname: Gilmozzi
authors.forename: Otto
authors.initials: O
authors.lastname: Berninghausen
authors.forename: Charlotte
authors.initials: C
authors.lastname: Ungewickell
authors.forename: Christian B
authors.initials: CB
authors.lastname: Gerhold
authors.forename: Kristina
authors.initials: K
authors.lastname: Lakomek
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
authors.forename: Roland
authors.initials: R
authors.lastname: Beckmann
authors.forename: Karl-Peter
authors.initials: KP
authors.lastname: Hopfner
mesh_terms: D042002:Chromatin Assembly and Disassembly; D013058:Mass Spectrometry; D008958:Models, Molecular; D009707:Nucleosomes / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: C483404:INO80 complex, S cerevisiae; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors