3E9F: Crystal Structure Short-form (residue1-113) Of Eaf3 Chromo Domain

Eaf3 is a component of both NuA4 histone acetyltransferase and Rpd3S histone deacetylase complexes in Saccharomyces cerevisiae. It is involved in the regulation of the global pattern of histone acetylation that distinguishes promoters from coding regions. Eaf3 contains a chromo domain at the N terminus that can bind to methylated Lys-36 of histone H3 (H3K36). We report here the crystal structures of the Eaf3 chromo domain in two truncation forms. Unlike the typical HP1 and Polycomb chromo domains, which contain a large groove to bind the modified histone tail, the Eaf3 chromo domain assumes an autoinhibited chromo barrel domain similar to the human MRG15 chromo domain. Compared with other chromo domains, the Eaf3 chromo domain contains a unique 38-residue insertion that folds into two short beta-strands and a long flexible loop to flank the beta-barrel core. Both isothermal titration calorimetry and surface plasmon resonance studies indicate that the interaction between the Eaf3 chromo domain and the trimethylated H3K36 peptide is relatively weak, with a K(D) of approximately 10(-4) m. NMR titration studies demonstrate that the methylated H3K36 peptide is bound to the cleft formed by the C-terminal alpha-helix and the beta-barrel core. Site-directed mutagenesis study and in vitro binding assay results show that the conserved aromatic residues Tyr-23, Tyr-81, Trp-84, and Trp-88, which form a hydrophobic pocket at one end of the beta-barrel, are essential for the binding of the methylated H3K36. These results reveal the molecular mechanism of the recognition and binding of the methylated H3K36 by Eaf3 and provide new insights into the functional roles of the Eaf3 chromo domain.
PDB ID: 3E9FDownload
MMDB ID: 67777
PDB Deposition Date: 2008/8/22
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 3E9F: monomeric; determined by author and by software (PISA)
Molecular Components in 3E9F
Label Count Molecule
Protein (1 molecule)
Chromatin Modification-related Protein Eaf3(Gene symbol: EAF3)
Molecule annotation
Chemical (1 molecule)
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