DAXX envelops a histone H3.3-H4 dimer for H3.3-specific recognition Journal Article
| Authors: | Elsässer, S. J.; Huang, H.; Lewis, P. W.; Chin, J. W.; Allis, C. D.; Patel, D. J. |
| Article Title: | DAXX envelops a histone H3.3-H4 dimer for H3.3-specific recognition |
| Abstract: | 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. © 2012 Macmillan Publishers Limited. All rights reserved. |
| Keywords: | mutation; protein conformation; cell cycle proteins; complex formation; protein; nuclear proteins; dna; amino acid sequence; molecular sequence data; protein multimerization; chromatin; histone h3; substrate specificity; adaptor proteins, signal transducing; crystal structure; models, molecular; crystallography, x-ray; water; conformation; histones; mutant; metazoa; chaperone; nucleosomes; histone h4; dimer; binding, competitive; daxx protein; metazoan; conservation genetics; histone chaperones |
| Journal Title: | Nature |
| Volume: | 491 |
| Issue: | 7425 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2012-11-22 |
| Start Page: | 560 |
| End Page: | 565 |
| Language: | English |
| DOI: | 10.1038/nature11608 |
| PROVIDER: | scopus |
| PUBMED: | 23075851 |
| PMCID: | PMC4056191 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 January 2013" - "CODEN: NATUA" - "Source: Scopus" |
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