PDBsum entry 2r10

Transcription

PDB id: 2r10

Contents

Protein chains

293 a.a. *

Ligands

EDO ×2

Waters ×411

* Residue conservation analysis

PDB id:

2r10

Name:

Transcription

Title:

Structure of an acetylated rsc4 tandem bromodomain histone chimera

Structure:

Chromatin structure-remodeling complex protein rsc4, linker, histone h3. Chain: a, b. Fragment: fusion protein comprises histone h3 (6-18) and rsc4 tbd (22-361). Synonym: remodel the structure of chromatin complex subunit 4. Engineered: yes. Mutation: yes

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Gene: rsc4. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.20Å R-factor: 0.199 R-free: 0.246

Authors:

A.P.Vandemark,M.M.Kasten,E.Ferris,A.Heroux,C.P.Hill,B.R.Cairns

Key ref:

A.P.VanDemark et al. (2007). Autoregulation of the rsc4 tandem bromodomain by gcn5 acetylation. Mol Cell, 27, 817-828. PubMed id: 17803945 DOI: 10.1016/j.molcel.2007.08.018

Date:

21-Aug-07 Release date: 30-Oct-07

Protein chains

Q02206  (RSC4_YEAST) -  Chromatin structure-remodeling complex subunit RSC4 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 625 a.a.

Struc: 293 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1016/j.molcel.2007.08.018

Mol Cell 27:817-828 (2007)

PubMed id: 17803945

Autoregulation of the rsc4 tandem bromodomain by gcn5 acetylation.

A.P.VanDemark, M.M.Kasten, E.Ferris, A.Heroux, C.P.Hill, B.R.Cairns.

ABSTRACT

An important issue for chromatin remodeling complexes is how their bromodomains recognize particular acetylated lysine residues in histones. The Rsc4 subunit of the yeast remodeler RSC contains an essential tandem bromodomain (TBD) that binds acetylated K14 of histone H3 (H3K14ac). We report a series of crystal structures that reveal a compact TBD that binds H3K14ac in the second bromodomain and, remarkably, binds acetylated K25 of Rsc4 itself in the first bromodomain. Endogenous Rsc4 is acetylated only at K25, and Gcn5 is identified as necessary and sufficient for Rsc4 K25 acetylation in vivo and in vitro. Rsc4 K25 acetylation inhibits binding to H3K14ac, and mutation of Rsc4 K25 results in altered growth rates. These data suggest an autoregulatory mechanism in which Gcn5 performs both the activating (H3K14ac) and inhibitory (Rsc4 K25ac) modifications, perhaps to provide temporal regulation. Additional regulatory mechanisms are indicated as H3S10 phosphorylation inhibits Rsc4 binding to H3K14ac peptides.

Selected figure(s)

Figure 1.
Figure 1. Structures of Rsc4
(A) Domain organization of Rsc4 (top) and crystallized constructs (bottom). Rsc4 structure is the following: bromodomain 1 (cyan), bromodomain 2 (blue), wing insertion (orange), and the binding region for RSC and the RNA polymerases (green) ([Kasten et al., 2004] and [Soutourina et al., 2006]). First and last ordered residues in the crystallized constructs are indicated with arrows. Acetylated lysine residues are indicated with a magenta dot (K14 of H3 and K25 of Rsc4).
(B) Orthogonal views of Rsc4(36–340) ribbon diagram. Secondary structures are labeled, and termini are indicated N and C. The asparagine and two tyrosine side chains from each bromodomain that are important for acetyl lysine binding are colored yellow. The wing insertion is colored orange.
(C) Rsc4 amino acid sequence with secondary structures indicated above. Residues not ordered in the Rsc4(36–340) structure are indicated with a dashed line. The red squares indicate interface residues between BD1 (residues 36–162) and BD2 (residues 163–320). The magenta circle indicates the site of acetylation (K25).

Figure 3.
Figure 3. Binding of Rsc4 K25ac in BD1
Acetylated K25 binds BD1 and orders flanking residues. The F[o] − F[c] map (3.0 × rmsd, green) and 2F[o] − F[c] map (1.2 × rmsd, gray) were phased from the protein model refined in the absence of residues 19–35. Residues involved in K25ac recognition are shown in yellow.

The above figures are reprinted from an Open Access publication published by Cell Press: Mol Cell (2007, 27, 817-828) copyright 2007.

Figures were selected by an automated process.