Structure of a Sir2 substrate, Alba, reveals a mechanism for deacetylation-induced enhancement of DNA binding.
The targeted acetylation status of histones and several other transcriptional regulatory proteins plays an important role in gene expression, although the mechanism for this is not well understood. As a model to understand how targeted acetylation may effect transcription, we determined the x-ray crystal structure of the chromatin protein Alba from Archaeoglobus fulgidus, a substrate for the Sir2 protein that deacetylates it at lysine 11 to promote DNA binding by Alba. The structure reveals a dimer of dimers in which the dimer-dimer interface is stabilized by several conserved hydrophobic residues as well as the lysine 11 target of Sir2. We show that, in solution, the mutation of these hydrophobic residues or lysine 11 disrupts dimer-dimer formation and decreases DNA-binding affinity. We propose that the in vivo deacetylation of lysine 11 of archaeal Alba by Sir2 promotes protein oligomerization for optimal DNA binding. Implications for the mechanism by which histone acetylation modulates gene expression are discussed.
The Wistar Institute and the Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Kehao
K
Zhao
Xiaomei
X
Chai
Ronen
R
Marmorstein
D000581:Amidohydrolases / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry*; D019611:Archaeoglobus fulgidus; D003432:Cross-Linking Reagents / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D019281:Dimerization; D008239:Lysine / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
D019843:Archaeal Proteins; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; C444360:Sso10b protein, Sulfolobus solfataricus; D004247:DNA; D000581:Amidohydrolases; D008239:Lysine