谱系特异性氨基酸定义了Rad51和Dmc1重组酶的原质子-原质子接口的功能属性
Mike Petassi1, Yeonoh Shin1, Aidan M Jessop1
1Department of Biochemistry & Molecular Biophysics, Columbia University Irving Medical Center, New York, NY, 10032, USA.
bioRxiv : the preprint server for biology
|December 16, 2024
概括
研究人员研究了Rad51和Dmc1的DNA重组酶,在Rad51中发现了保存的芳香残留物,但没有Dmc1. 这种差异解释了它们在DNA修复中的独特进化路径和功能.
科学领域:
- 分子生物学分子生物学
- 进化生物学 进化生物学
- 结构生物学 结构生物学
背景情况:
- 细胞有两个Rad51/RecA家族的DNA重组:Rad51 (分裂和半分裂) 和Dmc1 (仅发生半分裂).
- 这些重组酶被认为是从一个古老的基因重复事件进化而来的.
研究的目的:
- 调查Rad51和Dmc1.1之间的进化关系.
- 要了解这两种DNA重组酶的功能分歧.
主要方法:
- 高分辨率冷电子显微镜 (CryoEM) 结构的Saccharomyces cerevisiae Rad51和Dmc1丝结合到单链DNA (ssDNA).
- 生物信息学分析.
- 自然序列变化的遗传分析.
- 深度突变分析.
主要成果:
- 化EM结构揭示了Rad51丝中几乎普遍存在的堆叠的界面芳香氨基酸残留物,这些残留物在Dmc1丝中不存在.
- 功能分析显示,Rad51.1.中的这些残留物具有高度受约束的序列空间.
- 相比之下,Dmc1在同等位置展示了一个广泛的功能景观.
结论:
- Rad51和Dmc1的独特进化轨迹是由保存的残留物和它们的功能景观的差异凸显出来的.
- 这些进化差异可能有助于Rad51和Dmc1.1之间的功能和机制差异.
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