Structure of Actin-related protein 8 and its contribution to nucleosome binding

Nucleic Acids Res. 2012 Nov;40(21):11036-46. doi: 10.1093/nar/gks842. Epub 2012 Sep 12.

Abstract

Nuclear actin-related proteins (Arps) are subunits of several chromatin remodelers, but their molecular functions within these complexes are unclear. We report the crystal structure of the INO80 complex subunit Arp8 in its ATP-bound form. Human Arp8 has several insertions in the conserved actin fold that explain its inability to polymerize. Most remarkably, one insertion wraps over the active site cleft and appears to rigidify the domain architecture, while active site features shared with actin suggest an allosterically controlled ATPase activity. Quantitative binding studies with nucleosomes and histone complexes reveal that Arp8 and the Arp8-Arp4-actin-HSA sub-complex of INO80 strongly prefer nucleosomes and H3-H4 tetramers over H2A-H2B dimers, suggesting that Arp8 functions as a nucleosome recognition module. In contrast, Arp4 prefers free (H3-H4)(2) over nucleosomes and may serve remodelers through binding to (dis)assembly intermediates in the remodeling reaction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry
  • Actins / metabolism
  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / chemistry
  • Amino Acid Sequence
  • Humans
  • Microfilament Proteins / chemistry*
  • Microfilament Proteins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism
  • Nucleosomes / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Sequence Alignment

Substances

  • ACTR8 protein, human
  • Actins
  • Arp4 protein, S cerevisiae
  • INO80 complex, S cerevisiae
  • Microfilament Proteins
  • Nuclear Proteins
  • Nucleosomes
  • Saccharomyces cerevisiae Proteins
  • Adenosine Triphosphate
  • Adenosine Triphosphatases

Associated data

  • PDB/4FO0