2YGV

Conserved N-terminal domain of the yeast Histone Chaperone Asf1 in complex with the C-terminal fragment of Rad53

Summary for 2YGV

• Entry DOI: 10.2210/pdb2ygv/pdb
• Related: 1DMZ 1FHQ 1FHR 1G3G 1G6G 1J4K 1J4L 1J4O 1J4P 1J4Q 1K2M 1K2N 1K3J 1K3N 1K3Q 1QU5 1ROC 2A0T 2HUE
• Descriptor: HISTONE CHAPERONE ASF1, SERINE/THREONINE-PROTEIN KINASE RAD53, SULFATE ION, ... (5 entities in total)
• Functional Keywords: chaperone-transferase complex, checkpoint, dna damage, chromatin, chaperone/transferase
• Biological source: SACCHAROMYCES CEREVISIAE (BAKER'S YEAST); More
• Cellular location: Nucleus: P32447 P22216
• Total number of polymer chains: 8
• Total formula weight: 81956.40

Authors

Jiao, Y.,Seeger, K.,Murciano, B.,Ledu, M.H.,Charbonnier, J.B.,Legrand, P.,Lautrette, A.,Gaubert, A.,Mousson, F.,Guerois, R.,Mann, C.,Ochsenbein, F. (deposition date: 2011-04-21, release date: 2012-02-15, Last modification date: 2023-12-20)

Primary citation

Jiao, Y.,Seeger, K.,Lautrette, A.,Gaubert, A.,Mousson, F.,Guerois, R.,Mann, C.,Ochsenbein, F.
Surprising Complexity of the Asf1 Histone Chaperone-Rad53 Kinase Interaction
Proc.Natl.Acad.Sci.USA, 109:2866-, 2012

PubMed Abstract: The histone chaperone Asf1 and the checkpoint kinase Rad53 are found in a complex in budding yeast cells in the absence of genotoxic stress. Our data suggest that this complex involves at least three interaction sites. One site involves the H3-binding surface of Asf11 with an as yet undefined surface of Rad53. A second site is formed by the Rad53-FHA1 domain binding to Asf1-T(270) phosphorylated by casein kinase II. The third site involves the C-terminal 21 amino acids of Rad53 bound to the conserved Asf1 N-terminal domain. The structure of this site showed that the Rad53 C-terminus binds Asf1 in a remarkably similar manner to peptides derived from the histone cochaperones HirA and CAF-I. We call this binding motif, (R/K)R(I/A/V) (L/P), the AIP box for Asf1-Interacting Protein box. Furthermore, C-terminal Rad53-F(820) binds the same pocket of Asf1 as does histone H4-F(100). Thus Rad53 competes with histones H3-H4 and cochaperones HirA/CAF-I for binding to Asf1. Rad53 is phosphorylated and activated upon genotoxic stress. The Asf1-Rad53 complex dissociated when cells were treated with hydroxyurea but not methyl-methane-sulfonate, suggesting a regulation of the complex as a function of the stress. We identified a rad53 mutation that destabilized the Asf1-Rad53 complex and increased the viability of rad9 and rad24 mutants in conditions of genotoxic stress, suggesting that complex stability impacts the DNA damage response.

PubMed: 22323608
DOI: 10.1073/PNAS.1106023109

Experimental method

X-RAY DIFFRACTION (2.94 Å)