PDBsum entry 2vnf

Cell cycle

PDB id: 2vnf

Contents

Protein chains

50 a.a. *

54 a.a. *

Ligands

ALA-ARG-THR-M3L-GLN-THR

ALA-ARG-THR-M3L-GLN-THR-ALA-ARG-LYS-SER

DTT

DTU

Metals

_ZN ×4

_NA

Waters ×127

* Residue conservation analysis

PDB id:

2vnf

Name:

Cell cycle

Title:

Molecular basis of histone h3k4me3 recognition by ing4

Structure:

Inhibitor of growth protein 4. Chain: a, c. Fragment: residues 187-245. Synonym: ing 4, p29ing4. Engineered: yes. Histone h3. Chain: b, d. Fragment: residues 2-11. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes. Organism_taxid: 9606

Resolution:

1.76Å R-factor: 0.160 R-free: 0.227

Authors:

A.Palacios,I.G.Munoz,D.Pantoja-Uceda,M.J.Marcaida,D.Torres, J.M.Martin-Garcia,I.Luque,G.Montoya,F.J.Blanco

Key ref:

A.Palacios et al. (2008). Molecular basis of histone H3K4me3 recognition by ING4. J Biol Chem, 283, 15956-15964. PubMed id: 18381289 DOI: 10.1074/jbc.M710020200

Date:

04-Feb-08 Release date: 01-Apr-08

Protein chain

Q9UNL4  (ING4_HUMAN) -  Inhibitor of growth protein 4 from Homo sapiens

Seq: 249 a.a.

Struc: 50 a.a.

Protein chain

Q9UNL4  (ING4_HUMAN) -  Inhibitor of growth protein 4 from Homo sapiens

Seq: 249 a.a.

Struc: 54 a.a.

DOI no: 10.1074/jbc.M710020200

J Biol Chem 283:15956-15964 (2008)

PubMed id: 18381289

Molecular basis of histone H3K4me3 recognition by ING4.

A.Palacios, I.G.Muñoz, D.Pantoja-Uceda, M.J.Marcaida, D.Torres, J.M.Martín-García, I.Luque, G.Montoya, F.J.Blanco.

ABSTRACT

The inhibitors of growth (ING) family of tumor suppressors consists of five homologous proteins involved in chromatin remodeling. They form part of different acetylation and deacetylation complexes and are thought to direct them to specific regions of the chromatin, through the recognition of H3K4me3 (trimethylated K4 in the histone 3 tail) by their conserved plant homeodomain (PHD). We have determined the crystal structure of ING4-PHD bound to H3K4me3, which reveals a tight complex stabilized by numerous interactions. NMR shows that there is a reduction in the backbone mobility on the regions of the PHD that participate in the peptide binding, and binding affinities differ depending on histone tail lengths Thermodynamic analysis reveals that the discrimination in favor of methylated lysine is entropy-driven, contrary to what has been described for chromodomains. The molecular basis of H3K4me3 recognition by ING4 differs from that of ING2, which is consistent with their different affinities for methylated histone tails. These differences suggest a distinct role in transcriptional regulation for these two ING family members because of the antagonistic effect of the complexes that they recruit onto chromatin. Our results illustrate the versatility of PHD fingers as readers of the histone code.

Selected figure(s)

Figure 1.
FIGURE 1. Three-dimensional crystal structure of the complex of ING4-PHD bound to H3[10]K4me3. A, overall structure with ING4-PHD shown in gray and H3[10]K4me3 shown in yellow stick representation. The location of the ING4 residues lining the binding grooves for histone 3 residues Ala^1, Arg^2, Thr^3, Lys^4, and Ser^10 is indicated with black labels. B, view of a 2(|F[o]| - |F[c]|) omit map at 1.76 Å contoured at 1 as a blue mesh. The omit map was calculated with the program OMIT in the CCP4 package (45). C, details of the β-sheet structure formed by H3 residues Arg^2–Thr^6 and ING4 residues Gly^207–Gly^211 with backbone hydrogen bonds in green. D, details of side chain interactions with hydrogen bonds and water molecules in green.

Figure 3.
FIGURE 3. Comparison of the structures of H3K4me3 peptides bound to ING4 and ING2 PHD. A, the crystal structure of ING4-PHD is shown as a gray surface with the bound H3[10]K4me3 in yellow and the superimposed H3[12]K4me3 from the corresponding ING2-PHD complex structure in green. Only H3 residues Ala^1 to Arg^8 are seen in the crystal of the ING2 complex (Protein Data Bank entry 2G6Q). Black labels indicate the C atoms of the peptide residues, whose positions are very similar in both peptides up to H3 Thr^6. B, surface representations of the PHD fingers of ING2 and ING4 bound to the histone peptides where the electrostatic potential is indicated by a gradient of red (negative charge) and blue (positive charge) colors. The positions of the homologous tyrosine residues 198 and 215 are indicated in ING4 and ING2, respectively.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2008, 283, 15956-15964) copyright 2008.

Figures were selected by an automated process.