Crystal structure of yeast Esa1 suggests a unified mechanism for catalysis and substrate binding by histone acetyltransferases.
Esa1 is the catalytic subunit of the NuA4 histone acetylase (HAT) complex that acetylates histone H4, and it is a member of the MYST family of HAT proteins that includes the MOZ oncoprotein and the HIV-1 Tat interacting protein Tip60. Here we report the X-ray crystal structure of the HAT domain of Esa1 bound to coenzyme A and investigate the protein's catalytic mechanism. Our data reveal that Esa1 contains a central core domain harboring a putative catalytic base, and flanking domains that are implicated in histone binding. Comparisons with the Gcn5/PCAF and Hat1 proteins suggest a unified mechanism of catalysis and histone binding by HAT proteins, whereby a structurally conserved core domain mediates catalysis, and sequence variability within a structurally related N- and C-terminal scaffold determines substrate specificity.
Yan
Y
Y
The Wistar Institute University of Pennsylvania, Philadelphia, PA 19104, USA.
Barlev
N A
NA
Haley
R H
RH
Berger
S L
SL
Marmorstein
R
R
D000123:Acetyltransferases / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D020134:Catalytic Domain; D003065:Coenzyme A / Q000737:chemistry / Q000378:metabolism*; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D005656:Fungal Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D015003:Yeasts / Q000201:enzymology* / Q000235:genetics
D005656:Fungal Proteins; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D000123:Acetyltransferases; C496551:Esa1 protein, S cerevisiae; D051548:Histone Acetyltransferases; D003065:Coenzyme A