1GUW

STRUCTURE OF THE CHROMODOMAIN FROM MOUSE HP1beta IN COMPLEX WITH THE LYSINE 9-METHYL HISTONE H3 N-TERMINAL PEPTIDE, NMR, 25 STRUCTURES

Summary for 1GUW

• Entry DOI: 10.2210/pdb1guw/pdb
• Related: 1AP0 1DZ1
• Descriptor: CHROMOBOX PROTEIN HOMOLOG 1, HISTONE H3.1 (2 entities in total)
• Functional Keywords: chromatin-binding, lysine methylation, heterochromatin, histone modification
• Biological source: MUS MUSCULUS (MOUSE); More
• Total number of polymer chains: 2
• Total formula weight: 10525.67

Authors

Nielsen, P.R.,Nietlispach, D.,Mott, H.R.,Callaghan, J.M.,Bannister, A.,Kouzarides, T.,Murzin, A.G.,Murzina, N.V.,Laue, E.D. (deposition date: 2002-02-01, release date: 2002-03-12, Last modification date: 2018-01-17)

Primary citation

Nielsen, P.R.,Nietlispach, D.,Mott, H.R.,Callaghan, J.M.,Bannister, A.,Kouzarides, T.,Murzin, A.G.,Murzina, N.V.,Laue, E.D.
Structure of the Hp1 Chromodomain Bound to Histone H3 Methylated at Lysine 9
Nature, 416:103-107, 2002

PubMed 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.

PubMed: 11882902
DOI: 10.1038/NATURE722

Experimental method

SOLUTION NMR