结合核酶对抗人体SIRT6的基因组H3脱乙化作用
Ekaterina Smirnova1,2,3,4, Emmanuelle Bignon5, Patrick Schultz1,2,3,4
1Department of Integrated Structural Biology, IGBMC, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.
eLife
|February 28, 2024
概括
赛尔图因6 (SIRT6) 结合于核体,而不是自由基因组. 它的结构揭示了它如何去乙化基因组H3尾巴以进行DNA修复和寿命调节.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 赛尔图因6 (SIRT6) 是一种依赖NAD+的脱乙酶,对DNA修复,代谢平衡和寿命至关重要.
- SIRT6独特地结合了核细胞体,与其他向自由基因素尾巴的sirtin不同,但机制尚不清楚.
研究的目的:
- 阐明SIRT6与核体结合的结构性基础及其激活组织脱乙烯化活性.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定与核体结合的人类SIRT6的结构.
- 分子动力学 (MD) 模拟来分析基因素尾相互作用和酶活性.
主要成果:
- 该结构揭示了SIRT6的指域与核酶体的酸性补丁挂.
- 罗斯曼折叠域与未包裹的DNA相互作用,将NAD+结合点定位在DNA出口附近,并促进H3尾部脱乙烯化.
- MD模拟证实SIRT6的活性位点已经准备好进行H3尾部脱乙烯化,即使是靠近基因组核的lysines.
结论:
- SIRT6的核细胞结合机制涉及与DNA和基因组分的特定相互作用.
- 这种相互作用促进了基因素H3尾部的脱乙基化,影响了基因调节和细胞过程.
- 这些发现为SIRT6在DNA修复和寿命调节中的作用提供了结构性的见解.
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