Publication Abstract from PubMed
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.
Structure of a human ASF1a-HIRA complex and insights into specificity of histone chaperone complex assembly.,Tang Y, Poustovoitov MV, Zhao K, Garfinkel M, Canutescu A, Dunbrack R, Adams PD, Marmorstein R Nat Struct Mol Biol. 2006 Oct;13(10):921-9. Epub 2006 Sep 17. PMID:16980972[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
