Structural highlights
Function
[ARP8_HUMAN] Plays an important role in the functional organization of mitotic chromosomes. Exhibits low basal ATPase activity, and unable to polymerize. Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA reoplication and probably DNA repair. Required for the recruitment of INO80 (and probably the INO80 complex) to sites of DNA damage. Strongly prefer nucleosomes and H3-H4 tetramers over H2A-H2B dimers, suggesting it may act as a nucleosome recognition module within the complex.
Publication Abstract from PubMed
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.
Structure of Actin-related protein 8 and its contribution to nucleosome binding.,Gerhold CB, Winkler DD, Lakomek K, Seifert FU, Fenn S, Kessler B, Witte G, Luger K, Hopfner KP Nucleic Acids Res. 2012 Sep 12. PMID:22977180[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gerhold CB, Winkler DD, Lakomek K, Seifert FU, Fenn S, Kessler B, Witte G, Luger K, Hopfner KP. Structure of Actin-related protein 8 and its contribution to nucleosome binding. Nucleic Acids Res. 2012 Sep 12. PMID:22977180 doi:http://dx.doi.org/10.1093/nar/gks842
