取决于营养信号的四分体结构重塑驱动了metazoan PASK的催化激活
Sajina Dhungel1, Michael Xiao1, Rajaian Pushpabai Rajesh1
1Department of Biology, University of Kentucky, Lexington, Kentucky 40502, USA.
bioRxiv : the preprint server for biology
|July 9, 2024
概括
科学家们发现了一种新的调节机制在metazoan PAS域调节激酶 (PASK) 中的Per-Arnt-Sim (PAS) 域. 这种对营养物质敏感的PAS-C域组合集成环境信号,影响激酶活性并提供治疗点.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 每个Arnt-Sim (PAS) 域对于感知代谢物和信号至关重要.
- 这些域通常具有并联PAS和PAS关联的C端 (PAC) 图案.
- 在元动物中PAS域的调节和结构动态仍然不完全理解.
研究的目的:
- 调查PAS域调节激酶 (PASK) 中的PAS域的序列结构关系.
- 在PASK.中确定新的监管机制和结构组合.
- 探索这些发现对信号整合和激酶调节的功能影响.
主要方法:
- 进化规模的序列分析.
- 域名映射 域名映射
- 基于深度学习的蛋白质结构预测.
- 对PASK (鱼类,鸟类,哺乳动物) 的正义分析进行比较分析.
- 残留水平交叉连接测定.
- 结构分化学结构分化学
主要成果:
- 在PASK中发现了一种新的,以前未被识别的第三个PAS域 (PAS-C),由远程分子内相互作用形成.
- 经过实验验证,PAS-C域组合被证明是对营养物质有反应的.
- PAS-C 域组合将营养感应与四级结构重组联系起来,稳定了 PASK 激酶的催化核心.
- 该组件作为环境信号的关键集成点,调节PASK激酶活性.
结论:
- 甲基动物PAS域通过调制的PAS和PAC动机相互作用表现出动态信号整合能力.
- PASK中的新型PAS-C域组件代表了多细胞系统的新监管层.
- 准PAS-C域组合为涉及PASK失调的疾病提供了潜在的治疗策略.
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