DAXX envelops a histone H3.3-H4 dimer for H3.3-specific recognition.
Publication Type:Journal Article
Source:Nature, Volume 491, Issue 7425, p.560-5 (2012)
Keywords:Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Binding, Competitive, Cell Cycle Proteins, Crystallography, X-Ray, DNA, Histone Chaperones, Histones, Humans, Models, Molecular, Molecular Sequence Data, Nuclear Proteins, Nucleosomes, Protein Conformation, Protein Multimerization, Substrate Specificity, Water
<p>Histone chaperones represent a structurally and functionally diverse family of histone-binding proteins that prevent promiscuous interactions of histones before their assembly into chromatin. DAXX is a metazoan histone chaperone specific to the evolutionarily conserved histone variant H3.3. Here we report the crystal structures of the DAXX histone-binding domain with a histone H3.3-H4 dimer, including mutants within DAXX and H3.3, together with in vitro and in vivo functional studies that elucidate the principles underlying H3.3 recognition specificity. Occupying 40% of the histone surface-accessible area, DAXX wraps around the H3.3-H4 dimer, with complex formation accompanied by structural transitions in the H3.3-H4 histone fold. DAXX uses an extended α-helical conformation to compete with major inter-histone, DNA and ASF1 interaction sites. Our structural studies identify recognition elements that read out H3.3-specific residues, and functional studies address the contributions of Gly 90 in H3.3 and Glu 225 in DAXX to chaperone-mediated H3.3 variant recognition specificity.</p>