PDBsum entry 2h14

Transcription

PDB id: 2h14

Contents

Protein chain

303 a.a. *

Waters ×531

* Residue conservation analysis

PDB id:

2h14

Name:

Transcription

Title:

Crystal of wdr5 (apo-form)

Structure:

Wd-repeat protein 5. Chain: a. Fragment: residues 22-334. Synonym: bmp2-induced 3-kb gene protein. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: wdr5. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.48Å R-factor: 0.159 R-free: 0.197

Authors:

J.F.Couture,E.Collazo,R.C.Trievel

Key ref:

J.F.Couture et al. (2006). Molecular recognition of histone H3 by the WD40 protein WDR5. Nat Struct Mol Biol, 13, 698-703. PubMed id: 16829960 DOI: 10.1038/nsmb1116

Date:

15-May-06 Release date: 11-Jul-06

Protein chain

P61964  (WDR5_HUMAN) -  WD repeat-containing protein 5 from Homo sapiens

Seq: 334 a.a.

Struc: 303 a.a.

DOI no: 10.1038/nsmb1116

Nat Struct Mol Biol 13:698-703 (2006)

PubMed id: 16829960

Molecular recognition of histone H3 by the WD40 protein WDR5.

J.F.Couture, E.Collazo, R.C.Trievel.

ABSTRACT

The WD40-repeat protein WDR5 is a conserved subunit of Trithorax (TRX) histone methyltransferase complexes. WDR5 has been reported to selectively bind dimethylated Lys4 (K4me2) in histone H3 to promote K4 trimethylation by TRX. To elucidate the basis of this binding specificity, we have determined the crystal structure of WDR5 bound to a histone H3 peptide bearing K4me2. The structure reveals that the N terminus of histone H3 binds as a 3(10)-helix in the central depression formed by the WD40 repeats. R2 in histone H3 is bound in the acidic channel in the protein's core, whereas K4me2 is solvent exposed and does not engage in direct interactions with WDR5. Functional studies confirm that WDR5 recognizes A1, R2 and T3 in histone H3 but has virtually identical affinities for the unmodified and mono-, di- and trimethylated forms of K4, demonstrating that it does not discriminate among different degrees of methylation of this residue.

Selected figure(s)

Figure 1.
Figure 1. Crystal structure of WDR5 bound to the N terminus of histone H3. (a) Two orthogonal views of the secondary structure of WDR5 with the -propeller blades and the N and C termini labeled. The distorted sixth -propeller is highlighted in green, and the carbon atoms of the histone H3 peptide are rendered in yellow. (b) Electrostatic surface of WDR5 showing the histone H3 binding cleft (blue and red denote positively and negatively charged regions, respectively). The histone H3 peptide is shown as in a.

Figure 2.
Figure 2. Recognition of the histone H3 N terminus by WDR5. (a) Stereo view of the simulated annealing F[o] - F[c] omit map (green). Electron density is contoured at 2.0 . Gray carbons, WDR5; yellow carbons, histone H3. Q5 in histone H3 was omitted from the image for clarity. (b) Schematic representation of the interactions observed between WDR5 and histone H3. Residues in the protein that engage in van der Waals contacts, hydrogen bonds or salt bridge interactions with histone H3 are shown. Hydrogen bonds and salt bridge interactions are delineated by orange dashed lines. (c) Superimposition of the histone H3–binding cleft of apo-WDR5 (green) and the WDR5–histone H3 complex (blue), showing structural rearrangements that occur upon histone binding.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2006, 13, 698-703) copyright 2006.

Figures were selected by an automated process.