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

2006; Nature Portfolio; Volume: 13; Issue: 10 Linguagem: Inglês

10.1038/nsmb1147

1545-9993

Yong Tang, Maxim Poustovoitov, Kehao Zhao, Megan Garfinkel, Adrian A. Canutescu, Roland L. Dunbrack, Peter D. Adams, Ronen Marmorstein,

Ubiquitin and proteasome pathways

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 β-hairpin that binds perpendicular to the strands of the β-sandwich of ASF1a, via β-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.