该PAS域的结构组合驱动了PASK元群的催化激活
Sajina Dhungel1, Michael Xiao1, Rajesh Rajaian Pushpabai1
1Department of Biology, University of Kentucky, Lexington, KY 40502.
概括
这项研究揭示了PAS域调节激酶 (PASK) 中一种新的营养感应机制,涉及动态结构重组. 这一发现扩大了对PAS域调节的理解,并提供了治疗点.
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:
- PAS域是保护的感觉模块,调节细胞反应.
- 通过PAS域调节的激酶 (PASK) 在细胞信号传递中起着关键作用.
- 规范性PAS域使用并列折叠和图案来进行信号传导.
研究的目的:
- 研究PAS域调节激酶 (PASK) 的结构和调节机制.
- 在PASK中识别新的PAS域并阐明它们的功能角色.
- 了解PASK如何整合环境信号,特别是营养素,以调节其激酶活性.
主要方法:
- 进化规模的域映射用于识别新的PAS域.
- 基于深度学习的结构建模来预测PASK架构.
- 生物化学测试以评估营养反应和四级结构重塑.
- 结构分析以确定PAS域的空间布局及其对激酶域的影响.
主要成果:
- 在PASK中确定了两个额外的PAS域:PAS-B和PAS-C,以及已知的PAS-A域.
- 发现了一个独特的PAS-C域结构,其中PAS折叠和PAC动机在空间上是分离的,但通过分子内相互作用功能地组装在一起.
- 证明PAS域组合对营养物质有反应,导致PASK中的四级结构变化.
- 表明这种对营养素敏感的结构重组将PAS-A放置在激酶激活循环附近,使其稳定并使催化激活成为可能.
结论:
- 通过动态结构组合,PASK利用了另一种PAS域调节模式,将营养感应与激酶活性联系起来.
- 这些发现扩大了已知的PAS领域的功能表及其信号集成机制.
- 这项研究提供了针对PAS域介导信号通路的潜在治疗策略的见解.
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