"活性ポリコンブ抑制複合体2"によるヒストンH3K27トリメチル化の構造的基礎"への応答
1Cecil H. and Ida Green Center for Reproductive Biology Sciences and Division of Basic Research, Department of Obstetrics and Gynecology and Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Science (New York, N.Y.)
|December 24, 2016
まとめ
ポリコンブ抑制複合体2 (PRC2) の結晶構造は,H3K27M癌変異ペプチドではなく,柔軟なリンク器領域を明らかにし,電子密度に適合する. この研究では,真のH3K27M配列に結合したctPRC2構造が提供され,代替解釈が支持されています.
科学分野:
- 生物化学
- 構造生物学
- エピジェネティクス
背景:
- ポリコンブ抑制複合体2 (PRC2) は重要な表遺伝子調節体である.
- H3K27M変異は小児の脳腫瘍と関連しています
- 以前のPRC2とH3K27Mの構造研究は,変異ペプチドの結合に関する矛盾した解釈をもたらした.
研究 の 目的:
- H3K27M がん変異ペプチドとのポリコンブ抑制複合体2 (PRC2) 相互作用の構造的基礎を解明する.
- 本物のH3K27M配列に結合したctPRC2の高解像度結晶構造を提供すること.
- 以前のctPRC2結晶構造における電子密度フィッティングの解釈を評価する.
主な方法:
- X線結晶学
- タンパク質発現と浄化
- 生化学的測定法
主要な成果:
- 本来のH3K27Mペプチドに結合したctPRC2の結晶構造を決定した.
- このデータは,H3K27Mペプチド自体よりも柔軟なリンク器領域がctPRC2結晶構造の電子密度に適しているという解釈を支持する.
- この発見は,PRC2に結合するH3K27Mの以前のモデルに異議を唱える.
結論:
- PRC2とのH3K27Mがん変異の相互作用は,主に柔軟なリンカー領域によって媒介されます.
- この構造的な洞察は 癌におけるPRC2の機能の理解を 洗練します
- この結合モードの機能的影響を探るため,さらなる研究が必要である.
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