2I32

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

Summary for 2I32

• Entry DOI: 10.2210/pdb2i32/pdb
• Descriptor: Anti-Silencing Factor 1 paralog a, Histone Regulatory homolog A (3 entities in total)
• Functional Keywords: histone deposition, chromatin regulation, histone chaperones, asf1, hira, caf-1, replication chaperone
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus : Q9Y294 P54198
• Total number of polymer chains: 4
• Total formula weight: 54106.06

Authors

Marmorstein, R.,Tang, Y. (deposition date: 2006-08-17, release date: 2006-09-19, Last modification date: 2023-08-30)

Primary citation

Tang, Y.,Poustovoitov, M.V.,Zhao, K.,Garfinkel, M.,Canutescu, A.,Dunbrack, R.,Adams, P.D.,Marmorstein, R.
Structure of a human ASF1a-HIRA complex and insights into specificity of histone chaperone complex assembly.
Nat.Struct.Mol.Biol., 13:921-929, 2006

PubMed Abstract: 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: 16980972
DOI: 10.1038/nsmb1147

Experimental method

X-RAY DIFFRACTION (2.7 Å)