解读乳酸脱酶的进化轨迹提供了对Allostery的新见解
Adeline Y Robin1, Céline Brochier-Armanet2, Quentin Bertrand1,3
1Université Grenoble Alpes, CNRS, CEA, IBS, F-38000 Grenoble, France.
Molecular biology and evolution
|October 5, 2023
概括
乳酸脱酶 (LDH) 酶进化了多种不同的调节机制. 这项研究揭示了蓝藻细菌LDH的意想不到的全激活,挑战了先前的进化假设,并确定了关键的氨基酸部位,这些部位负责真核细胞的调节变化.
科学领域:
- 生物化学 生物化学
- 进化生物学 进化生物学
- 结构生物学 结构生物学
背景情况:
- 乳酸脱酶 (LDH) 对于无氧代谢至关重要,它将酸盐转化为乳酸盐.
- 了解LDH进化解释了真核生物多样化和监管修改.
- 以前的研究将真核细胞LDH全调节损失与N端延伸联系起来.
研究的目的:
- 调查真核细胞中LDHs的进化起源和多样化.
- 阐明LDHs中全性调节的结构和功能基础.
- 为了确定关键的分子决定因素减弱质激活在真核细胞LDHs.
主要方法:
- 具有真核生物样特征的蓝藻细菌LDHs的序列分析.
- 对于Cyanobacterium aponinum LDH的生物化学和晶体学表征.
- 位点定向突变发生,以测试特定氨基酸位置在全调节中的作用.
主要成果:
- 杆菌aponinum LDH表现出意想不到的同型和异型激活,这是所有菌酶的特征.
- 结晶学结构显示了R-活性和T-无活性状态,这与全性LDHs典型.
- 确定了两个特定的氨基酸位置,而不是N终端延伸,在真核LDH中丧失全激活的关键.
结论:
- 这项研究提出了一个新的LDH进化场景,将调节性质与结构和突变模式统一起来.
- 关键氨基酸替代,而不是N端扩展,可能导致了真核细胞LDHs中全性能力的丧失.
- 这些发现提供了对LDH演变及其监管多样性的基础机制的全面理解.
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