人类PRC2与其辅因子AEBP2和JARID2的结构。
Structures of human PRC2 with its cofactors AEBP2 and JARID2.
作者信息
Kasinath Vignesh, Faini Marco, Poepsel Simon, Reif Dvir, Feng Xinyu Ashlee, Stjepanovic Goran, Aebersold Ruedi, Nogales Eva
机构信息
QB3 Institute, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
出版信息
Science. 2018 Feb 23;359(6378):940-944. doi: 10.1126/science.aar5700. Epub 2018 Jan 18.
Transcriptionally repressive histone H3 lysine 27 methylation by Polycomb repressive complex 2 (PRC2) is essential for cellular differentiation and development. Here we report cryo-electron microscopy structures of human PRC2 in a basal state and two distinct active states while in complex with its cofactors JARID2 and AEBP2. Both cofactors mimic the binding of histone H3 tails. JARID2, methylated by PRC2, mimics a methylated H3 tail to stimulate PRC2 activity, whereas AEBP2 interacts with the RBAP48 subunit, mimicking an unmodified H3 tail. SUZ12 interacts with all other subunits within the assembly and thus contributes to the stability of the complex. Our analysis defines the complete architecture of a functionally relevant PRC2 and provides a structural framework to understand its regulation by cofactors, histone tails, and RNA.
多梳抑制复合物2（PRC2）介导的转录抑制性组蛋白H3赖氨酸27甲基化对于细胞分化和发育至关重要。在此，我们报告了处于基础状态以及与辅因子JARID2和AEBP2结合时两种不同活性状态下的人PRC2的冷冻电子显微镜结构。两种辅因子均模拟组蛋白H3尾巴的结合。被PRC2甲基化的JARID2模拟甲基化的H3尾巴以刺激PRC2活性，而AEBP2与RBAP48亚基相互作用，模拟未修饰的H3尾巴。SUZ12与组装体中的所有其他亚基相互作用，从而有助于复合物的稳定性。我们的分析确定了功能相关的PRC2的完整结构，并提供了一个结构框架来理解其受辅因子、组蛋白尾巴和RNA的调控机制。
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