PDBsum entry 2g6q

Gene regulation, apoptosis

PDB id: 2g6q

Contents

Protein chain

52 a.a. *

Ligands

ALA-ARG-THR-M3L-GLN-THR-ALA-ARG

Metals

_ZN ×2

Waters ×32

* Residue conservation analysis

PDB id:

2g6q

Name:

Gene regulation, apoptosis

Title:

Crystal structure of ing2 phd finger in complex with h3k4me3 peptide

Structure:

Inhibitor of growth protein 2. Chain: a. Fragment: phd domain (residues 204-263). Synonym: p33ing2, inhibitor of growth 1-like protein, ing1lp, p32. Engineered: yes. H3k4me3 peptide. Chain: b. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: ing2, ing1l. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: h3k4me3 is chemically synthesized

Biol. unit:

Dimer (from PQS)

Resolution:

2.00Å R-factor: 0.223 R-free: 0.231

Authors:

P.V.Pena,R.Zhao,T.G.Kutateladze

Key ref:

P.V.Peña et al. (2006). Molecular mechanism of histone H3K4me3 recognition by plant homeodomain of ING2. Nature, 442, 100-103. PubMed id: 16728977 DOI: 10.1038/nature04814

Date:

24-Feb-06 Release date: 11-Jul-06

Protein chain

Q9ESK4  (ING2_MOUSE) -  Inhibitor of growth protein 2 from Mus musculus

Seq: 281 a.a.

Struc: 52 a.a.

DOI no: 10.1038/nature04814

Nature 442:100-103 (2006)

PubMed id: 16728977

Molecular mechanism of histone H3K4me3 recognition by plant homeodomain of ING2.

P.V.Peña, F.Davrazou, X.Shi, K.L.Walter, V.V.Verkhusha, O.Gozani, R.Zhao, T.G.Kutateladze.

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.

Selected figure(s)

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.

Figures were selected by the author.