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.
Mesh Terms:
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
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
Nature
Date: Nov. 22, 2012
PubMed ID: 23075851
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