1NFJ

Structure of a Sir2 substrate, alba, reveals a mechanism for deactylation-induced enhancement of DNA-binding

Summary for 1NFJ

• Entry DOI: 10.2210/pdb1nfj/pdb
• Related: 1NFH
• Descriptor: conserved hypothetical protein AF1956 (2 entities in total)
• Functional Keywords: sir2, alba, hdac, gene regulation, transcription
• Biological source: Archaeoglobus fulgidus
• Cellular location: Cytoplasm (Probable): O28323
• Total number of polymer chains: 1
• Total formula weight: 9908.44

Authors

Zhao, K.,Chai, X.,Marmorstein, R. (deposition date: 2002-12-15, release date: 2003-08-05, Last modification date: 2024-02-14)

Primary citation

Zhao, K.,Chai, X.,Marmorstein, R.
Structure of a Sir2 substrate, alba, reveals a mechanism for deacetylation-induced enhancement of DNA-binding
J.Biol.Chem., 278:26071-26077, 2003

PubMed Abstract: 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.

PubMed: 12730210
DOI: 10.1074/jbc.M303666200

Experimental method

X-RAY DIFFRACTION (2 Å)