 |
PDBsum entry 2g6q
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Gene regulation, apoptosis
|
PDB id
|
|
|
|
2g6q
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Molecular mechanism of histone h3k4me3 recognition by plant homeodomain of ing2.
|
|
|
Authors
|
|
P.V.Peña,
F.Davrazou,
X.Shi,
K.L.Walter,
V.V.Verkhusha,
O.Gozani,
R.Zhao,
T.G.Kutateladze.
|
|
|
Ref.
|
|
Nature, 2006,
442,
100-103.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Covalent modifications of histone tails have a key role in regulating chromatin
structure and controlling transcriptional activity. In eukaryotes, histone H3
trimethylated at lysine 4 (H3K4me3) is associated with active chromatin and gene
expression. We recently found that plant homeodomain (PHD) finger of tumour
suppressor ING2 (inhibitor of growth 2) binds H3K4me3 and represents a new
family of modules that target this epigenetic mark. The molecular mechanism of
H3K4me3 recognition, however, remains unknown. Here we report a 2.0 A resolution
structure of the mouse ING2 PHD finger in complex with a histone H3 peptide
trimethylated at lysine 4. The H3K4me3 tail is bound in an extended conformation
in a deep and extensive binding site consisting of elements that are conserved
among the ING family of proteins. The trimethylammonium group of Lys 4 is
recognized by the aromatic side chains of Y215 and W238 residues, whereas the
intermolecular hydrogen-bonding and complementary surface interactions,
involving Ala 1, Arg 2, Thr 3 and Thr 6 of the peptide, account for the PHD
finger's high specificity and affinity. Substitution of the binding site
residues disrupts H3K4me3 interaction in vitro and impairs the ability of ING2
to induce apoptosis in vivo. Strong binding of other ING and YNG PHD fingers
suggests that the recognition of H3K4me3 histone code is a general feature of
the ING/YNG proteins. Elucidation of the mechanisms underlying this novel
function of PHD fingers provides a basis for deciphering the role of the ING
family of tumour suppressors in chromatin regulation and signalling.
|
|
|
|
|
|
|
|
Figure 1.
Figure 1: Structure of ING2 PHD finger in complex with a histone
H3 peptide trimethylated at Lys 4. a, The PHD finger is shown
as a solid surface with the binding site residues coloured and
labelled. The Lys 4 and Arg 2 binding grooves are in brown and
yellow, respectively. The histone peptide is shown as a
ball-and-stick model with C, O and N atoms coloured green, red
and blue, respectively. b, Ribbon diagram of the structure.
Dashed lines represent intermolecular hydrogen bonds.
|
|
Figure 2.
Figure 2: ING2 PHD finger recognizes H3K4me3. a, Six
superimposed ^1H,^15N heteronuclear single quantum coherence
(HSQC) spectra of PHD (0.2 mM) collected during titration of
H3K4me3 peptide are colour-coded according to the ligand
concentration (inset). b, The histogram displays normalized
^1H,^15N chemical shift changes observed in the corresponding
(a) spectra of the PHD finger. The normalized^27 chemical shift
change was calculated using the equation [(   H)^2
+ ( N/5)^2]^0.5,
where is
the chemical shift in parts per million (p.p.m.). Coloured bars
indicate significant change being greater than average plus
one-half standard deviation.
|
|
|
|
|
|
The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2006,
442,
100-103)
copyright 2006.
|
|
|
|
|
|
|
