PDBsum entry 2qxv

Gene regulation

PDB id

2qxv

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Contents

			Protein chains

					352 a.a. *


					29 a.a. *

			Waters ×390

* Residue conservation analysis

PDB id:

2qxv

Links

Name:

Gene regulation

Title:

Structural basis of ezh2 recognition by eed

Structure:

Embryonic ectoderm development. Chain: a. Fragment: residues in database 81-441. Synonym: eed. Engineered: yes. Enhancer of zeste homolog 2. Chain: b. Fragment: residues 39-68. Synonym: ezh2, enx-1.

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: heed. Expressed in: escherichia coli. Expression_system_taxid: 511693. Gene: ezh2, enx1h.

Resolution:

1.82Å

R-factor:

0.185

R-free:

0.218

Authors:

Z.Han

Key ref:

Z.Han et al. (2007). Structural basis of EZH2 recognition by EED. Structure, 15, 1306-1315. PubMed id: 17937919 DOI: 10.1016/j.str.2007.08.007

Date:

13-Aug-07

Release date:

28-Aug-07

PROCHECK

	Headers

	References

Protein chain

Q921E6 (EED_MOUSE) - Polycomb protein EED from Mus musculus

Seq: Struc:					441 a.a. 352 a.a.

Protein chain

Q61188 (EZH2_MOUSE) - Histone-lysine N-methyltransferase EZH2 from Mus musculus

Seq: Struc:

Seq: Struc:					746 a.a. 29 a.a.

Key:

PfamA domain

Secondary structure

CATH domain



		Enzyme reactions

Enzyme class 2:

Chain A: E.C.?

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Enzyme class 3:

Chain B: E.C.2.1.1.356 - [histone H3]-lysine(27) N-trimethyltransferase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

L-lysyl₂₇-[histone H3] + 3 S-adenosyl-L-methionine = N₆,N₆,N₆- trimethyl-L-lysyl₂₇-[histone H3] + 3 S-adenosyl-L-homocysteine + 3 H⁺

L-lysyl(27)-[histone H3]	+	3 × S-adenosyl-L-methionine	=	N(6),N(6),N(6)- trimethyl-L-lysyl(27)-[histone H3]	+	3 × S-adenosyl-L-homocysteine	+	3 × H(+)

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1016/j.str.2007.08.007	Structure 15:1306-1315 (2007)
PubMed id: 17937919

Structural basis of EZH2 recognition by EED.
Z.Han, X.Xing, M.Hu, Y.Zhang, P.Liu, J.Chai.

ABSTRACT

The WD-repeat domain is a highly conserved recognition module in eukaryotes involved in diverse cellular processes. It is still not well understood how the bottom of a WD-repeat domain recognizes its binding partners. The WD-repeat-containing protein EED is one component of the PRC2 complex that possesses histone methyltransferase activity required for gene repression. Here we report the crystal structure of EED in complex with a 30 residue peptide from EZH2. The structure reveals that the peptide binds to the bottom of the WD-repeat domain of EED. The structural determinants of EZH2-EED interaction are present not only in EZH2 and EZH1 but also in its Drosophila homolog E(Z), suggesting that the recognition of ESC by E(Z) in Drosophila employs similar structural motifs. Structure-based mutagenesis identified critical residues from both EED and EZH2 for their interaction. The structure presented here may provide a template for understanding of how WD-repeat proteins recognize their interacting proteins.

Selected figure(s)



	Figure 3. Figure 3. EBD Binds to a Well-Defined Groove at the Bottom of EED (A) A schematic representation of EED and the EED-binding domain in EZH2 (EBD) (residues 39–68). EED and EBD are shown in cyan and orange, respectively. (B) Electrostatic complementarity between EED and EBD. Both EED and EBD are represented in electrostatic surface. The positive, negative, and neutral surfaces are colored in blue, red, and white, respectively. To distinguish between EED and EBD, EBD is also shown as a cartoon (cyan). (C) Shape complementarity between EED and EBD. EED and EBD are represented in mesh and surface, respectively.		Figure 5. Figure 5. Structural Comparison of the EED-EBD Complex and Gβγ Dimer Superposition of the EED-EBD complex and Gβγ dimer (Protein Data Bank ID code: 1TBG2) is viewed from two different angles. EED, EBD, Gβ, and Gγ are colored in orange, cyan, magenta, and light pink, respectively. The two labeled residues shown in stick form are from EBD (marine) and Gγ (slate).

Figures were selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21336826

A.Grzenda, T.Ordog, and R.Urrutia (2011).
Polycomb and the emerging epigenetics of pancreatic cancer.

J Gastrointest Cancer, 42, 100-111.

20451393

C.U.Stirnimann, E.Petsalaki, R.B.Russell, and C.W.Müller (2010).
WD40 proteins propel cellular networks.

Trends Biochem Sci, 35, 565-574.

20974918

C.Xu, C.Bian, W.Yang, M.Galka, H.Ouyang, C.Chen, W.Qiu, H.Liu, A.E.Jones, F.MacKenzie, P.Pan, S.S.Li, H.Wang, and J.Min (2010).
Binding of different histone marks differentially regulates the activity and specificity of polycomb repressive complex 2 (PRC2).

Proc Natl Acad Sci U S A, 107, 19266-19271.

PDB codes:

3jpx 3jzg 3jzh 3jzn 3k26 3k27

20174665

S.Rato, S.Maia, P.M.Brito, L.Resende, C.F.Pereira, C.Moita, R.P.Freitas, J.Moniz-Pereira, N.Hacohen, L.F.Moita, and J.Goncalves (2010).
Novel HIV-1 knockdown targets identified by an enriched kinases/phosphatases shRNA library using a long-term iterative screen in Jurkat T-cells.

PLoS One, 5, e9276.

19738629

J.A.Simon, and R.E.Kingston (2009).
Mechanisms of polycomb gene silencing: knowns and unknowns.

Nat Rev Mol Cell Biol, 10, 697-708.

19345089

J.Müller, and P.Verrijzer (2009).
Biochemical mechanisms of gene regulation by polycomb group protein complexes.

Curr Opin Genet Dev, 19, 150-158.

19767730

R.Margueron, N.Justin, K.Ohno, M.L.Sharpe, J.Son, W.J.Drury, P.Voigt, S.R.Martin, W.R.Taylor, V.De Marco, V.Pirrotta, D.Reinberg, and S.J.Gamblin (2009).
Role of the polycomb protein EED in the propagation of repressive histone marks.

Nature, 461, 762-767.

PDB codes:

3iiw 3iiy 3ij0 3ij1 3ijc

18302803

D.Rakotobe, S.Violot, S.S.Hong, P.Gouet, and P.Boulanger (2008).
Mapping of immunogenic and protein-interacting regions at the surface of the seven-bladed beta-propeller domain of the HIV-1 cellular interactor EED.

Virol J, 5, 32.

18693240

P.Joshi, E.A.Carrington, L.Wang, C.S.Ketel, E.L.Miller, R.S.Jones, and J.A.Simon (2008).
Dominant Alleles Identify SET Domain Residues Required for Histone Methyltransferase of Polycomb Repressive Complex 2.

J Biol Chem, 283, 27757-27766.

19026781

R.Margueron, G.Li, K.Sarma, A.Blais, J.Zavadil, C.L.Woodcock, B.D.Dynlacht, and D.Reinberg (2008).
Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms.

Mol Cell, 32, 503-518.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.