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 liked 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 ASFA1a'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.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 930563
- Report Number(s):
- BNL-80720-2008-JA; TRN: US200904%%788
- Journal Information:
- Nature Structural and Molecular Biology, Vol. 13, Issue 10; ISSN 1545-9993
- Country of Publication:
- United States
- Language:
- English
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