A conserved motif common to the histone acetyltransferase Esa1 and the histone deacetylase Rpd3.
Post-translational modification of histones enables dynamic regulation of chromatin structure in eukaryotes. Histone acetyltransferase (HAT) and histone deacetylase (HDAC) modify the N-terminal tails of histones by adding or removing acetyl groups to specific lysine residues. A particular pair of HAT (Esa1) and HDAC (Rpd3) is proposed to modify the same lysine residue in vitro and in vivo. Thus, HAT and HDAC might have similar structural and functional motifs. Here we show that HAT (Esa1 family) and HDAC (Rpd3 family) have similar amino acid stretches in the primary structures through evolution. We refer to this region as the "ER (Esa1-Rpd3) motif." In the tertiary structure of Esa1, the ER motif is located near the active center. In Rpd3, for which the tertiary structure remains unclear, we demonstrate that the ER motif contains the same secondary structure as found in Esa1 by circular dichroism analysis. We did alanine-scanning mutagenesis and found that the ER motif regions of Esa1 or Rpd3 are required for HAT activity of Esa1 or HDAC activity of Rpd3, respectively. Our discovery of the ER motif present in the pair of enzymes (HAT and HDAC) indicates that HAT and HDAC have common structural bases, although they catalyze the reaction with opposite functions.
The Horikoshi Gene Selector Project, Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology Corporation (JST), 5-9-6 Tokodai, Tsukuba, Ibaraki 300-2635 Japan.
Naruhiko
N
Adachi
Akatsuki
A
Kimura
Masami
M
Horikoshi
D000123:Acetyltransferases / Q000737:chemistry* / Q000235:genetics; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001483:Base Sequence; D002942:Circular Dichroism; D017124:Conserved Sequence; D017931:DNA Primers; D051548:Histone Acetyltransferases; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D029701:Saccharomyces cerevisiae Proteins; D000123:Acetyltransferases; D051548:Histone Acetyltransferases