Structural dynamics of the chromo-shadow domain and chromodomain of HP1 bound to histone H3K9 methylated peptide, as measured by site-directed spin-labeling EPR spectroscopy
Structural dynamics of the chromo-shadow domain and chromodomain of HP1 bound to histone H3K9 methylated peptide, as measured by site-directed spin-labeling EPR spectroscopy
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通过定点自旋标记 EPR 光谱测量与组蛋白 H3K9 甲基化肽结合的 HP1 的染色阴影结构域和染色结构域的结构动力学
DOI：
10.1016/j.bbrc.2021.06.010
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发表时间：
2021
影响因子：
3.1
通讯作者：
Arata Toshiaki
中科院分区：
文献类型：
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作者：
Suetake Isao;Nakazawa Shigeaki;Sato Kazunobu;Mutoh Risa;Mishima Yuichi;Kawakami Toru;Takei Toshiki;Watanabe Mikio;Sakai Norio;Fujiwara Toshimichi;Takui Takeji;Miyata Makoto;Shinohara Akira;Hojo Hironobu;Arata Toshiaki
利用自旋标记电子顺磁共振和脉冲双共振技术，在纳秒和纳米尺度上研究了人HP 1蛋白质中异染色质形成所必需的染色质阴影结构域（CSD）和染色质结构域（CD）的结构动力学.距离测量表明，人HP 1 α和HP 1 γ的自旋标记CSD紧密地二聚化。与在失活状态的裂变酵母HP 1中观察到的CD-CD相互作用不同（Canzio et al.，2013），HP 1 α和HP 1 γ的两个CD在空间上彼此分离，动态地移动的，并且准备用于组蛋白上的H3 K9-三甲基（me 3）的布朗搜索。CD与H3 K9 me 3的复合物形成由于降低的扩散常数而减缓了域的动力学。全长HP 1 α的CSD迁移率显著低于HP 1 γ（约1.3倍），表明人HP 1 α的固定化构象显示出自失活状态。HP 1 α和HP 1 γ形成非活性构象的差异性质可能与其在细胞异染色质形成中的生理作用有关。
The structural dynamics of the chromo-shadow domain (CSD) and chromodomain (CD) of human HP1 proteins essential for heterochromatin formation were investigated at the nanosecond and nanometer scales by site-directed spin labeling electron paramagnetic resonance and pulsed double resonance spectroscopy. Distance measurements showed that the spin-labeled CSD of human HP1α and HP1γ tightly dimerizes. Unlike CD-CD interaction observed in fission yeast HP1 in an inactivated state (Canzio et al., 2013), the two CDs of HP1α and HP1γ were spatially separated from each other, dynamically mobile, and ready for a Brownian search for H3K9-tri-methyl(me3) on histones. Complex formation of the CD with H3K9me3 slowed dynamics of the domain due to a decreased diffusion constant. CSD mobility was significantly (∼1.3-fold) lower in full-length HP1α than in HP1γ, suggesting that the immobilized conformation of human HP1α shows an auto-inactivated state. Differential properties of HP1α and HP1γ to form the inactive conformation could be relevant to its physiological role in the heterochromatin formation in a cell.