論文 - 詳細
| RRC ID | 83373 |
|---|---|
| 著者 | Furukawa A, Yonezawa K, Negami T, Yoshimura Y, Hayashi A, Nakayama JI, Adachi N, Senda T, Shimizu K, Terada T, Shimizu N, Nishimura Y. |
| タイトル | A dynamic structural unit of phase-separated heterochromatin protein 1α as revealed by integrative structural analyses. |
| ジャーナル | Nucleic Acids Res |
| Abstract |
The heterochromatin protein HP1α consists of an N-terminal disordered tail (N-tail), chromodomain (CD), hinge region (HR), and C-terminal chromo shadow domain (CSD). While CD binds to the lysine9-trimethylated histone H3 (H3K9me3) tail in nucleosomes, CSD forms a dimer bridging two nucleosomes with H3K9me3. Phosphorylation of serine residues in the N-tail enhances both H3K9me3 binding and liquid-liquid phase separation (LLPS) by HP1α. We have used integrative structural methods, including nuclear magnetic resonance, small-angle X-ray scattering (SAXS), and multi-angle-light scattering combined with size-exclusion chromatography, and coarse-grained molecular dynamics simulation with SAXS, to probe the HP1α dimer and its CSD deletion monomer. We show that dynamic intra- and intermolecular interactions between the N-tails and basic segments in CD and HR depend on N-tail phosphorylation. While the phosphorylated HP1α dimer undergoes LLPS via the formation of aggregated multimers, the N-tail phosphorylated mutant without CSD still undergoes LLPS, but its structural unit is a dynamic intermolecular dimer formed via the phosphorylated N-tail and a basic segment at the CD end. Furthermore, we reveal that mutation of this basic segment in HP1α affects the size of heterochromatin foci in cultured mammalian cells, suggesting that this interaction plays an important role in heterochromatin formation in vivo. |
| 巻・号 | 53(6) |
| 公開日 | 2025-3-20 |
| DOI | 10.1093/nar/gkaf154 |
| PII | 8089752 |
| PMID | 40138713 |
| MeSH | Animals Chromobox Protein Homolog 5* / chemistry Chromobox Protein Homolog 5* / metabolism Chromosomal Proteins, Non-Histone* / chemistry Chromosomal Proteins, Non-Histone* / metabolism Heterochromatin / chemistry Heterochromatin / metabolism Histones / chemistry Histones / genetics Histones / metabolism Humans Molecular Dynamics Simulation* Nucleosomes / chemistry Nucleosomes / metabolism Phosphorylation Protein Binding Protein Domains Protein Multimerization Scattering, Small Angle* X-Ray Diffraction |
| IF | 11.502 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 15 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | NIH3T3-3(RCB0150) |