PDBsum entry 2dx8

Metal binding protein

PDB id: 2dx8

Contents

Protein chains

60 a.a. *

Metals

_ZN ×4

Waters ×67

* Residue conservation analysis

PDB id:

2dx8

Name:

Metal binding protein

Title:

Crystal structure analysis of the phd domain of the transcription coactivator pygophus

Structure:

Pygopus homolog 1. Chain: a, b. Fragment: phd domain. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Other_details: cell-free

Resolution:

2.70Å R-factor: 0.199 R-free: 0.255

Authors:

B.Padmanabhan,S.Yokoyama,Riken Structural Genomics/proteomics Initiative (Rsgi)

Key ref:

Y.Nakamura et al. (2007). Crystal structure analysis of the PHD domain of the transcription co-activator Pygopus. J Mol Biol, 370, 80-92. PubMed id: 17499269 DOI: 10.1016/j.jmb.2007.04.037

Date:

24-Aug-06 Release date: 15-May-07

Protein chains

Q9D0P5  (PYGO1_MOUSE) -  Pygopus homolog 1 from Mus musculus

Seq: 417 a.a.

Struc: 60 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/j.jmb.2007.04.037

J Mol Biol 370:80-92 (2007)

PubMed id: 17499269

Crystal structure analysis of the PHD domain of the transcription co-activator Pygopus.

Y.Nakamura, T.Umehara, H.Hamana, Y.Hayashizaki, M.Inoue, T.Kigawa, M.Shirouzu, T.Terada, A.Tanaka, B.Padmanabhan, S.Yokoyama.

ABSTRACT

The Wnt/beta-catenin signaling pathway plays important roles in animal development and cancer. Pygopus (Pygo) and Legless (Lgs) are recently discovered core components of the Wnt/beta-catenin transcription machinery complex, and are crucially involved in the regulation of the transcription of the Arm/beta-catenin and T cell factors (TCF). Lgs/Bcl9 functions as an adaptor between Pygo and Arm/beta-catenin. Here, we report the first crystal structure of the plant homeodomain (PHD) finger of Pygopus (Pygo1 PHD), a Pygo family member, which is essential for the association with Lgs/Bcl9. The Pygo1 PHD structure forms a canonical PHD finger motif, stabilized by two Zn ions coordinated in a cross-brace scheme. Surprisingly, the Pygo1 PHD domain forms a dimer in both the crystals and solution. This is the first structural evidence for dimerization among the known PHD domain structures. The dimer formation occurs by the interactions of antiparallel beta-sheets between the symmetry-related beta3 strands of the monomers. The Pygo1 PHD dimer interface mainly comprises hydrophobic residues. Interestingly, some of the interface residues, such as Met372, Thr373, Ala376 and Leu380, are reportedly important for the association with Lgs/Bcl9 and are also critical for transcriptional activation. The M372A and L380D mutants, and several surrounding mutants such as S385A and A386D, showed decreased ability to form dimers and to interact with the homology domain 1 (HD1) of Lgs/Bcl9. These results suggest that the Pygo1 PHD dimerization is functionally important for Lgs/Bcl9 recognition as well as for the regulation of the Wnt/beta-catenin signaling pathway.

Selected figure(s)

Figure 2.
Figure 2. Tertiary structure of the mouse Pygo1 PHD domain. (a) A representation of the electron density map. A section of the final σ (a)-weighted 2F[o]-F[c] map at 2.8 Å resolution, contoured at 1.0σ. (b) Ribbon representation of the mouse Pygo1 PHD domain (blue to red). The two zinc ions, Zn1 and Zn2, are shown as blue spheres, and the residues participating in the Zn coordination system, as well as the conserved Trp388, are shown as stick models. Structural Figures were generated with PyMOL (ver. 0.99) [www.pymol.org]. Figure 2. Tertiary structure of the mouse Pygo1 PHD domain. (a) A representation of the electron density map. A section of the final σ (a)-weighted 2F[o]-F[c] map at 2.8 Å resolution, contoured at 1.0σ. (b) Ribbon representation of the mouse Pygo1 PHD domain (blue to red). The two zinc ions, Zn1 and Zn2, are shown as blue spheres, and the residues participating in the Zn coordination system, as well as the conserved Trp388, are shown as stick models. Structural Figures were generated with PyMOL (ver. 0.99) [www.pymol.org].

Figure 6.
Figure 6. A comparison of the Pygo1 PHD domain with the ING2 and BPTF PHD domains. (a) A superposition of the Pygo1 PHD domain (pink) onto the ING2 (green) and BPTF (cyan) PHD domains complexed with the H3K4me3 histone peptides. The H3K4me3 peptides are shown by stick models and the trimethylated lysines are labeled. (b) A representative electrostatic surface potential of the ING2 complex. The H3K4me3 peptide is shown by a stick model. (c) An electrostatic surface potential of the Pygo1 PHD domain (chain A only) near the H3K4me3 binding region. Panels (b) and (c) are in the same orientation as in (a). The surfaces are colored blue and red for positive and negative electrostatic surface potential, respectively. Figure 6. A comparison of the Pygo1 PHD domain with the ING2 and BPTF PHD domains. (a) A superposition of the Pygo1 PHD domain (pink) onto the ING2 (green) and BPTF (cyan) PHD domains complexed with the H3K4me3 histone peptides. The H3K4me3 peptides are shown by stick models and the trimethylated lysines are labeled. (b) A representative electrostatic surface potential of the ING2 complex. The H3K4me3 peptide is shown by a stick model. (c) An electrostatic surface potential of the Pygo1 PHD domain (chain A only) near the H3K4me3 binding region. Panels (b) and (c) are in the same orientation as in (a). The surfaces are colored blue and red for positive and negative electrostatic surface potential, respectively.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 370, 80-92) copyright 2007.

Figures were selected by an automated process.