3P7J

Drosophila HP1a chromo shadow domain

3P7J の概要

• エントリーDOI: 10.2210/pdb3p7j/pdb
• 分子名称: Heterochromatin protein 1, GLYCEROL (3 entities in total)
• 機能のキーワード: heterochromatin protein 1, chromo shadow domain, gene silencing, epigenetics, transcription
• 由来する生物種: Drosophila melanogaster (Fruit fly)
• 細胞内の位置: Nucleus: P05205
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 20162.50

構造登録者

Kim, D.,Chruszcz, M.,Minor, W.,Khorasanizadeh, S. (登録日: 2010-10-12, 公開日: 2011-02-02, 最終更新日: 2023-09-06)

主引用文献

Mendez, D.L.,Kim, D.,Chruszcz, M.,Stephens, G.E.,Minor, W.,Khorasanizadeh, S.,Elgin, S.C.
The HP1a Disordered C Terminus and Chromo Shadow Domain Cooperate to Select Target Peptide Partners.
Chembiochem, 12:1084-1096, 2011

PubMed Abstract: Drosophila melanogaster heterochromatin protein 1a (HP1a) is essential for compacted heterochromatin structure and the associated gene silencing. Its chromo shadow domain (CSD) is well known for binding to peptides that contain a PXVXL motif. Heterochromatin protein 2 (HP2) is a non-histone chromosomal protein that associates with HP1a in the pericentric heterochromatin, telomeres, and the fourth chromosome. Using NMR spectroscopy, fluorescence polarization, and site-directed mutagenesis, we identified an LCVKI motif in HP2 that binds to the HP1a CSD. The binding affinity of the HP2 fragment is approximately two orders of magnitude higher than that of peptides from PIWI (with a PRVKV motif), AF10 (with a PLVVL motif), or CG15356 (with LYPLL and LSIVA motifs). To delineate differential interactions of the HP1a CSD, we characterized its structure, backbone dynamics, and dimerization constant. We found that the dimerization constant is bracketed by the affinities of HP2 and PIWI, which dock to the same HP1a homodimer surface. This suggests that HP2, but not PIWI, interaction can drive the homodimerization of HP1a. Interestingly, the integrity of the disordered C-terminal extension (CTE) of HP1a is essential for discriminatory binding, whereas swapping the PXVXL motifs does not confer specificity. Serine phosphorylation at the peptide binding surface of the CSD is thought to regulate heterochromatin assembly. Glutamic acid substitution at these sites destabilizes HP1a dimers, but improves the interaction with both binding partners. Our studies underscore the importance of CSD dimerization and cooperation with the CTE in forming distinct complexes of HP1a.

PubMed: 21472955
DOI: 10.1002/cbic.201000598

実験手法

X-RAY DIFFRACTION (2.3 Å)