Nature Structural & Molecular Biology
- 13, 921 - 929 (2006)
Published online: 17 September 2006; | doi:10.1038/nsmb1147
Structure of a human ASF1a–HIRA complex and insights into specificity of histone chaperone complex assemblyYong Tang1, 4, Maxim V Poustovoitov2, 3, 4, Kehao Zhao1, Megan Garfinkel2, Adrian Canutescu2, Roland Dunbrack2, Peter D Adams2 & Ronen Marmorstein11
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA. 2
The Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. 3
Russian State Medical University, Moscow 117 869, Russia. 4
These authors contributed equally to this work.
Correspondence should be addressed to Ronen Marmorstein marmor@wistar.org or Peter D Adams peter.adams@fccc.edu 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  -hairpin that binds perpendicular to the strands of the -sandwich of ASF1a, via -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.
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