通过同进化统计建模和深度突变扫描,了解B1β-乳酸酶中的表观网络
J Z Chen1, M Bisardi2,3, D Lee1
1Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.
Nature communications
|September 30, 2024
概括
进化蛋白家族使用表观网络来容忍突变. 对B1金属β-乳酸酶的研究揭示了广泛的表皮病,约1/3的突变是表皮病性,影响蛋白质进化.
科学领域:
- 生物化学和分子生物学
- 进化生物学 进化生物学
- 结构生物学 结构生物学
背景情况:
- 蛋白质家族在保持结构和功能的同时演变出序列分歧.
- 内部分子相互作用的表观网络可以缓解进化过程中的有害突变.
- 跨蛋白质家族的表观性网络的全面分析是有限的.
研究的目的:
- 在B1金属β-乳酸酶中对表皮状网络进行全家族分析.
- 结合实验和计算方法来量化表现症.
- 为了确定表皮性残留物的结构和功能作用.
主要方法:
- 在NDM-1和VIM-2同类物体上进行深度突变扫描 (DMS).
- 在100个同类物体上使用直接合分析 (DCA) 的in silico DMS.
- 实验和计算数据的比较分析.
主要成果:
- 在DMS实验中,大约三分之一的同等突变是表观突变的.
- 直接合分析 (DCA) 表明,在整个家族中,耐受性突变存在显著差异.
- 在中间残留埋葬,平衡包装和自由的地区观察到最强烈的表皮病.
- 入的残留物表现出不同的行为,表明复杂的表观性网络.
结论:
- 在蛋白质家族进化中,表观症很普遍,可以量化.
- 中间残留物埋葬对于形成表皮性网络至关重要.
- 深入的残留物是复杂的表皮状网络的关键组成部分,稳定蛋白质功能.
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