DAXX envelops a histone H3.3-H4 dimer for H3.3-specific recognition.
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.
Pubmed ID: 23075851 RIS Download
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