 |
PDBsum entry 2r0v
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transcription
|
PDB id
|
|
|
|
2r0v
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Autoregulation of the rsc4 tandem bromodomain by gcn5 acetylation.
|
|
|
Authors
|
|
A.P.Vandemark,
M.M.Kasten,
E.Ferris,
A.Heroux,
C.P.Hill,
B.R.Cairns.
|
|
|
Ref.
|
|
Mol Cell, 2007,
27,
817-828.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
|
|
|
|
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.
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
