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在静音信息调节器异染色素复合体内的新型相互作用可以促进子单元之间的通信和基因抑制

Jenna Kotz^1,2,3, E J Martz^1,2,3, Maya Nelson¹

¹Department of Biochemistry and Molecular Genetics, University of Colorado, Denver - Anschutz Medical Campus.

bioRxiv : the preprint server for biology

|January 7, 2025

概括

酵母中的静音信息调节器复合体 (SIRc) 使用Sir2和Sir4之间的一种新型相互作用,从扩散基因脱乙烯化转向稳定的染色质紧缩,从而实现基因抑制.

科学领域:

分子生物学分子生物学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
染色体生物学染色体生物学

背景情况:

具有较小基因组的生物经常利用多个子单元蛋白质复合体来执行各种功能.
酵母无声信息调节器复合体 (SIRc) 调节所有核心异染色素功能,包括基因素脱乙和染色素紧缩.
虽然已知SIRc的脱乙基化和压缩作用,但由于结构数据有限,这些状态之间的过渡机制仍然不清楚.

研究的目的:

阐明SIRc从动态扩散状态转变为稳定的染色质紧缩的机制.
确定SIRc.内部对内部复杂通信的结构洞察力.

主要方法:

交联质谱法 (XL-MS) 用于分析溶液中的蛋白质-蛋白质相互作用.
结构分析的重点是识别SIRc.内部的子单位间相互作用.

主要成果:

在Sir2脱乙酶和Sir4支架子单元之间发现了一种新的子单元间相互作用.
这种相互作用涉及Sir4的线圈-线圈域,它也结合了Sir3的压缩子单元,形成了一个关键的相互作用枢纽.
在这个枢纽内保存的Sir2残留物参与感知脱乙状态并与Sir4相互作用,这表明它在特定物种的功能中发挥了作用.

结论:

鉴定的Sir2-Sir4相互作用物理地将SIRc.的脱乙基化和紧缩状态联系在一起.
这种相互作用枢纽的突变会损害异色抑制,这表明它在传达脱乙烯化完成以启动紧缩过程中的重要性.
这项研究揭示了一种涉及单一复合体内主要活动过渡的阶段性机制,用于表观遗传基因抑制.

关键词:

在HDAC的基础上,HDAC是复杂的SIR和SIR复合体.交叉连接质谱学质谱学表观遗传学是指表观遗传学.这里是Sirtuin.酵母酵母是一种酵母.

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