Article
- The EMBO Journal (2004) 23, 489 - 499
- doi:10.1038/sj.emboj.7600088
Published online: 5 February 2004
Subject Categories:
Structural basis of HP1/PXVXL motif peptide interactions and HP1 localisation to heterochromatin
Abarna Thiru1, Daniel Nietlispach1, Helen R Mott1, Mitsuru Okuwaki2, Debbie Lyon2, Peter R Nielsen1, Miriam Hirshberg1, Alain Verreault2, Natalia V Murzina1,3 and Ernest D Laue1,3
- Department of Biochemistry, Cambridge Centre for Molecular Recognition, University of Cambridge, Cambridge, UK
- Clare Hall Laboratories, London Research Institute, Cancer Research UK, South Mimms, UK
- The coordinates have been deposited in the RCSB PDB (accession number 1S4Z)
Correspondence to:
Natalia V Murzina, Department of Biochemistry, Cambridge Centre for Molecular Recognition, University of Cambridge, 80 Tennis Court Road, Cambridge CB1 1GA, UK. Tel.: +44 1223 333 677; Fax: +44 1223 766002; E-mail: nm@mole.bio.cam.ac.uk
Ernest D Laue, Department of Biochemistry, Cambridge Centre for Molecular Recognition, University of Cambridge, 80 Tennis Court Road, Cambridge CB1 1GA, UK. Tel.: +44 1223 333 677; Fax: +44 1223 766002; E-mail: e.d.laue@bioc.cam.ac.uk
Received 8 August 2003; Accepted 23 December 2003
Abstract
HP1 family proteins are adaptor molecules, containing two related chromo domains that are required for chromatin packaging and gene silencing. Here we present the structure of the chromo shadow domain from mouse HP1
bound to a peptide containing a consensus PXVXL motif found in many HP1 binding partners. The shadow domain exhibits a novel mode of peptide recognition, where the peptide binds across the dimer interface, sandwiched in a -sheet between strands from each monomer. The structure allows us to predict which other shadow domains bind similar PXVXL motif-containing peptides and provides a framework for predicting the sequence specificity of the others. We show that targeting of HP1 to heterochromatin requires shadow domain interactions with PXVXL-containing proteins in addition to chromo domain recognition of Lys-9-methylated histone H3. Interestingly, it also appears to require the simultaneous recognition of two Lys-9-methylated histone H3 molecules. This finding implies a further complexity to the histone code for regulation of chromatin structure and suggests how binding of HP1 family proteins may lead to its condensation.
Keywords:
- chromatin localisation,
- chromo domain,
- heterochromatin,
- heterochromatin protein 1,
- NMR spectroscopy,
- protein structure
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