PDBsum entry: 1guw

Chromatin-binding

PDB id: 1guw

Contents

Protein chains

73 a.a. *

18 a.a. *

* Residue conservation analysis

PDB id:

1guw

Name:

Chromatin-binding

Title:

Structure of the chromodomain from mouse hp1beta in complex with the lysine 9-methyl histone h3 n-terminal peptide, nmr, 25 structures

Structure:

Histone h3.1. Chain: b. Fragment: n-terminal tail, residues 1-18. Synonym: histone h3, nuclear protein, chromosomal protein, DNA-binding, nucleosome core, multigene family, methylation. Engineered: yes. Other_details: lysines 4 and 9 have been modified to n (epsilon)-dimethyl-lysine.

Source:

Synthetic: yes. Mus musculus. Mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 511693. Other_details: both chemically sythesized peptide and peptide obtained from expression in bacteria were used.. Expression_system_taxid: 469008.

NMR struc:

25 models

Authors:

P.R.Nielsen,D.Nietlispach,H.R.Mott,J.M.Callaghan, A.Bannister,T.Kouzarides,A.G.Murzin,N.V.Murzina,E.D.Laue

Key ref:

P.R.Nielsen et al. (2002). Structure of the HP1 chromodomain bound to histone H3 methylated at lysine 9. Nature, 416, 103-107. PubMed id: 11882902 DOI: 10.1038/nature722

Date:

01-Feb-02 Release date: 12-Mar-02

Protein chain

P83917  (CBX1_MOUSE) -  Chromobox protein homolog 1

Seq: 185 a.a.

Struc: 73 a.a.*

Protein chain

P68431  (H31_HUMAN) -  Histone H3.1

Seq: 136 a.a.

Struc: 18 a.a.*

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Cellular component: nucleus (3 terms)
• Biological process: chromatin assembly or disassembly (2 terms)
• Biochemical function: chromatin binding (2 terms)

DOI no: 10.1038/nature722

Nature 416:103-107 (2002)

PubMed id: 11882902

Structure of the HP1 chromodomain bound to histone H3 methylated at lysine 9.

P.R.Nielsen, D.Nietlispach, H.R.Mott, J.Callaghan, A.Bannister, T.Kouzarides, A.G.Murzin, N.V.Murzina, E.D.Laue.

ABSTRACT

Specific modifications to histones are essential epigenetic markers---heritable changes in gene expression that do not affect the DNA sequence. Methylation of lysine 9 in histone H3 is recognized by heterochromatin protein 1 (HP1), which directs the binding of other proteins to control chromatin structure and gene expression. Here we show that HP1 uses an induced-fit mechanism for recognition of this modification, as revealed by the structure of its chromodomain bound to a histone H3 peptide dimethylated at Nzeta of lysine 9. The binding pocket for the N-methyl groups is provided by three aromatic side chains, Tyr21, Trp42 and Phe45, which reside in two regions that become ordered on binding of the peptide. The side chain of Lys9 is almost fully extended and surrounded by residues that are conserved in many other chromodomains. The QTAR peptide sequence preceding Lys9 makes most of the additional interactions with the chromodomain, with HP1 residues Val23, Leu40, Trp42, Leu58 and Cys60 appearing to be a major determinant of specificity by binding the key buried Ala7. These findings predict which other chromodomains will bind methylated proteins and suggest a motif that they recognize.

Selected figure(s)

Figure 2.
Figure 2: The interface between the chromodomain and the methylated peptide. a, Tyr 21, Trp 42 and Phe 45 form a 'hydrophobic box' that binds the N-methyl groups. The methyl lysine side chain binds along the surface of Trp 42 and Thr 51, whereas Glu 53 and Asn 57 contact the C end. b, Gln 5 interacts with the N terminus of the -helix and Arg 8 interacts with a patch of acidic residues to help structure the flexible N-terminal tail. c, Ala 7 binds in the core of the chromodomain, making contacts with residues Val 23, Leu 40, Trp 42, Leu 58 and Cys 60. In a, b and c, side chains of the histone H3 peptide are red and interacting residues in the chromodomain are green.

Figure 3.
Figure 3: Sequence comparisons and residues involved in complex formation. a, Chromodomain alignment numbered for mouse HP1 . Residues important for methyl lysine recognition are blue (N-methyl groups) and light blue (Lys 9 side chain or backbone). Residues that make contacts with the K-2 position of the peptide (see text) are shown in yellow (HP1 family) or grey (others). The two segments of HP1 that form the walls of the peptide-binding groove are indicated by red lines. -strands are indicated by green arrows and the -helix by a blue cylinder. The blue dots indicate the positions of conserved bulges in 1. Conserved hydrophobic residues that define the fold and the borders of the turn between the -strand and the -helix (Pro 54 and Cys 60, respectively) are boxed. The regions in MSL3 and MOF1 that do not conform with a canonical chromodomain fold are shown in small letters. Sequences are labelled by species name (Mm, Mus musculus; Dm, Drosophila melanogaster; Xl, Xenopus laevis; Hs, Homo sapiens; Sp, Schizosaccharomyces pombe; Ce, Caenorhabditis elegans; Tt, Tetrahymena thermophila; At, Arabidopsis thaliana), followed by protein name, residue range and GenBank accession number. Produced using Alscript27. b, The sequence of the N-terminal tail of histone H3. Up arrows denote side chains that point into the chromodomain core; down arrows denote surface side chains. The right panel shows the N-terminal histone H3 and H4 sequences aligned around the lysines. The key K-2 position is shown in red and the lysines in green.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2002, 416, 103-107) copyright 2002.

Figures were selected by the author.