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Structure of a human ASF1a-HIRA complex and insights into specificity of histone chaperone complex assembly.

Human HIRA, ASF1a, ASF1b and CAF-1 are evolutionally conserved histone chaperones that form multiple functionally distinct chromatin-assembly complexes, with roles linked to diverse nuclear process, such as DNA replication and formation of heterochromatin in senescent cells. We report the crystal structure of an ASF1a-HIRA heterodimer and a biochemical dissection of ASF1a's mutually exclusive interactions with HIRA and the p60 subunit of CAF-1. The HIRA B domain forms an antiparallel beta-hairpin that binds perpendicular to the strands of the beta-sandwich of ASF1a, via beta-sheet, salt bridge and van der Waals contacts. The N- and C-terminal regions of ASF1a and ASF1b determine the different affinities of these two proteins for HIRA, by contacting regions outside the HIRA B domain. CAF-1 p60 also uses B domain-like motifs for binding to ASF1a, thereby competing with HIRA. Together, these studies begin to define the molecular determinants of assembly of functionally diverse macromolecular histone chaperone complexes.

Pubmed ID: 16980972


  • Tang Y
  • Poustovoitov MV
  • Zhao K
  • Garfinkel M
  • Canutescu A
  • Dunbrack R
  • Adams PD
  • Marmorstein R


Nature structural & molecular biology

Publication Data

October 5, 2006

Associated Grants

  • Agency: NIA NIH HHS, Id: P01 AG031862
  • Agency: NIA NIH HHS, Id: P01 AG031862-010001
  • Agency: NIGMS NIH HHS, Id: R01 GM060293
  • Agency: NIGMS NIH HHS, Id: R01 GM060293-01
  • Agency: NIGMS NIH HHS, Id: Y1 GM-0080-3

Mesh Terms

  • Amino Acid Sequence
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Histone Chaperones
  • Histones
  • Humans
  • Models, Molecular
  • Molecular Chaperones
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Tertiary
  • Sensitivity and Specificity
  • Structure-Activity Relationship
  • Transcription Factors
  • Transfection