2IO5

Crystal structure of the CIA- histone H3-H4 complex

Summary for 2IO5

• Entry DOI: 10.2210/pdb2io5/pdb
• Descriptor: ASF1A protein, Histone H3.1, Histone H4 (3 entities in total)
• Functional Keywords: histone, chaperone, chaperone-structural protein complex, chaperone/structural protein
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P84233 P62799
• Total number of polymer chains: 3
• Total formula weight: 46380.07

Authors

Natsume, R.,Akai, Y.,Horikoshi, M.,Senda, T. (deposition date: 2006-10-10, release date: 2007-02-27, Last modification date: 2023-10-25)

Primary citation

Natsume, R.,Eitoku, M.,Akai, Y.,Sano, N.,Horikoshi, M.,Senda, T.
Structure and function of the histone chaperone CIA/ASF1 complexed with histones H3 and H4.
Nature, 446:338-341, 2007

PubMed Abstract: CIA (CCG1-interacting factor A)/ASF1, which is the most conserved histone chaperone among the eukaryotes, was genetically identified as a factor for an anti-silencing function (Asf1) by yeast genetic screening. Shortly after that, the CIA-histone-H3-H4 complex was isolated from Drosophila as a histone chaperone CAF-1 stimulator. Human CIA-I/II (ASF1a/b) was identified as a histone chaperone that interacts with the bromodomain-an acetylated-histone-recognizing domain-of CCG1, in the general transcription initiation factor TFIID. Intensive studies have revealed that CIA/ASF1 mediates nucleosome assembly by forming a complex with another histone chaperone in human cells and yeast, and is involved in DNA replication, transcription, DNA repair and silencing/anti-silencing in yeast. CIA/ASF1 was shown as a major storage chaperone for soluble histones in proliferating human cells. Despite all these biochemical and biological functional analyses, the structure-function relationship of the nucleosome assembly/disassembly activity of CIA/ASF1 has remained elusive. Here we report the crystal structure, at 2.7 A resolution, of CIA-I in complex with histones H3 and H4. The structure shows the histone H3-H4 dimer's mutually exclusive interactions with another histone H3-H4 dimer and CIA-I. The carboxy-terminal beta-strand of histone H4 changes its partner from the beta-strand in histone H2A to that of CIA-I through large conformational change. In vitro functional analysis demonstrated that CIA-I has a histone H3-H4 tetramer-disrupting activity. Mutants with weak histone H3-H4 dimer binding activity showed critical functional effects on cellular processes related to transcription. The histone H3-H4 tetramer-disrupting activity of CIA/ASF1 and the crystal structure of the CIA/ASF1-histone-H3-H4 dimer complex should give insights into mechanisms of both nucleosome assembly/disassembly and nucleosome semi-conservative replication.

PubMed: 17293877
DOI: 10.1038/nature05613

Experimental method

X-RAY DIFFRACTION (2.7 Å)