DOI: 10.1126/science.1069473. Structure of HP1 Chromodomain Bound to a Lysine 9-Methylated Histone H3 Tail

Structure of HP1 Chromodomain Bound to a Lysine 9-Methylated Histone H3 Tail

10.1126/science.1069473

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

The chromodomain of the HP1 family of proteins recognizes histone tails with specifically methylated lysines. Here, we present structural, energetic, and mutational analyses of the complex between the Drosophila HP1 chromodomain and the histone H3 tail with a methyllysine at residue 9, a modification associated with epigenetic silencing. The histone tail inserts as a β strand, completing the β-sandwich architecture of the chromodomain. The methylammonium group is caged by three aromatic side chains, whereas adjacent residues form discerning contacts with one face of the chromodomain. Comparison of dimethyl- and trimethyllysine-containing complexes suggests a role for cation-π and van der Waals interactions, with trimethylation slightly improving the binding affinity.

Bibliography

Jacobs, S. A., & Khorasanizadeh, S. (2002). Structure of HP1 Chromodomain Bound to a Lysine 9-Methylated Histone H3 Tail. Science, 295(5562), 2080â2083.

Authors 2

Steven A. Jacobs (first)
Sepideh Khorasanizadeh (additional)

References 22 Referenced 705

Harp J. M., Hanson B. L., Timm D. E., Bunick G. J., Acta Cryst. D56, 1513 (2000). / Acta Cryst. by Harp J. M. (2000)
10.1038/38444
10.1126/science.1063127
10.1038/35065138
M. Lachner D. O'Carroll
10.1038/35065132
10.1126/science.1060118
10.1093/emboj/20.18.5232
10.1038/35087620
Supplementary data are available on Science Online at www.sciencemag.org/cgi/content/full/1069473/DC1.
10.1146/annurev.biophys.26.1.259
10.1093/emboj/16.9.2473
10.1016/S0960-9822(99)00260-2
10.1016/0003-2697(91)90045-U
10.1073/pnas.96.17.9459
10.1016/0022-2836(88)90606-7
Single-letter abbreviations for the amino acid residues are as follows: A Ala; C Cys; D Asp; E Glu; F Phe; G Gly; H His; I Ile; K Lys; L Leu; M Met; N Asn; P Pro; Q Gln; R Arg; S Ser; T Thr; V Val; W Trp; and Y Tyr.
S. A. Jacobs S. Khorasanizadeh unpublished observations.
10.1073/pnas.96.26.14967
10.1038/35030169
10.1093/emboj/19.7.1587
We thank F. Rastinejad for access to the Pharmacology X-Ray Diffraction Laboratory C. D. Allis for continued support and encouragement and M. F. Summers for access to an isothermal titration calorimetry instrument. Peptide synthesis was supported by grant GM63959-01 to C. D. Allis.

Dates

Type	When
Created	23 years ago (July 27, 2002, 1:35 a.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 4:47 p.m.)
Indexed	2 weeks, 5 days ago (Aug. 6, 2025, 8:17 a.m.)
Issued	23 years, 5 months ago (March 15, 2002)
Published	23 years, 5 months ago (March 15, 2002)
Published Print	23 years, 5 months ago (March 15, 2002)

Funders 0

None

BibTeX

@article{Jacobs_2002, title={Structure of HP1 Chromodomain Bound to a Lysine 9-Methylated Histone H3 Tail}, volume={295}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1069473}, DOI={10.1126/science.1069473}, number={5562}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Jacobs, Steven A. and Khorasanizadeh, Sepideh}, year={2002}, month=mar, pages={2080–2083} }

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