PDBsum entry 1nfh

Gene regulation

PDB id: 1nfh

Contents

Protein chains

86 a.a. *

Waters ×85

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Structure of a sir2 substrate, Alba, Reveals a mechanism for deacetylation-Induced enhancement of DNA binding.

Authors

K.Zhao, X.Chai, R.Marmorstein.

Ref.

J Biol Chem, 2003, 278, 26071-26077. [DOI no: 10.1074/jbc.M303666200]

PubMed id

12730210

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.

Figure 1.
FIG. 1. Structure of Af-Alba. Structure of the Alba monomer (a), dimer (b), and tetramer (c) in the crystals.

Figure 5.
FIG. 5. Model for DNA binding by Alba. a, model for how the Af-Alba tetramer binds DNA. b, electrostatic surface of the Af-Alba tetramer modeled on DNA. Blue, red, and white represent the degree of electropositive, electronegative, and neutral surface potential, respectively.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 26071-26077) copyright 2003.