单质卡斯帕斯的顺序展开机制
1Department of Biology, University of Texas at Arlington, Arlington, Texas 76019, United States.
Biochemistry
|June 20, 2023
概括
珊瑚石揭示了保存的折叠景观和依赖pH的调节. 这项研究揭示了单体和二元酶亚家族的演化,这对细胞亡至关重要.
科学领域:
- 生物化学 生物化学
- 进化生物学 进化生物学
- 分子生物学分子生物学
背景情况:
- 卡斯帕酶是重要的蛋白酶,调节细胞发育和细胞亡.
- 异位性囊存在于单体 (发起者) 或二次体 (效应者) 亚家族,具有不同的激活机制.
- 来自共同祖先的类亚家族的进化分歧尚未完全理解.
研究的目的:
- 为了研究从珊瑚物种单体石的折叠景观和稳定性.
- 了解单体和二元酶亚家族之间的进化关系.
- 探索单体体的pH依赖的构造变化和调节.
主要方法:
- 在广泛的pH范围 (3-10.5) 中检查了蛋白质折叠稳定性.
- 使用了分子动力学模拟,有限蛋白质分解和MALDI-TOF质谱.
- 分析了珊瑚和人类鱼的进化分歧.
主要成果:
- 珊瑚石在生理pH附近表现出高稳定性 (∼15 kcal mol-1).
- 蛋白质在平衡状态下通过两个部分折叠的中间体展开.
- 保存的全位介导着pH依赖的形状变化,小子单元在大子单元之前展开.
结论:
- 所有caspases共享一个保存的折叠景观.
- 保存的全位允许对物种进行特定调节.
- 稳定的二维卡斯帕斯的演变可能与稳定小子单元有关.
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