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一个AlphaFold指导模型用于CaMKII互动组的进化

Salman T Khawaja¹, Maham Hamid¹, Thomas S Reese²

¹Department of Life Sciences, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences, Lahore, 54792, Pakistan.

bioRxiv : the preprint server for biology

|September 19, 2025

概括

和素依赖蛋白激酶II (CaMKII) 相互作用组进化揭示了物种间保存的分子相互作用. 它的架构,最初是用于神经分泌,专门用于哺乳动物的突触信号传递.

科学领域:

神经科学是一个神经科学.
分子生物学分子生物学
进化生物学进化生物学

背景情况:

神经元功能依赖于卡尔莫杜林依赖蛋白激酶II (CaMKII) 相互作用.
在Ca2+激活时,CaMKII的激酶域与调节剂和基质结合.
了解CaMKII的进化轨迹是它多样化的角色的关键.

研究的目的:

分析 CaMKII 相互作用体在不同生物体中的演变.
为了研究CaMKII分子相互作用的保存.
追踪CaMKII的功能专业化,从神经分泌到突触信号传递.

主要方法:

分析了40多个3D原子结构和CaMKII目标复合体的模型.
结合表面重叠,能量挫折和折叠演变的比较分析.
利用转录基因组数据库进行Ca2+反应调节和基质同位素化研究.

主要成果:

CaMKII的分子互动组显示了跨物种的显著保护,包括Trichoplax adhaerans.
在更简单的生物体中,CaMKII激活机制是不变的,但与基质的共同表达减少.
从哺乳动物到更简单的生物,观察到CaMKII和基质共同表达的逐渐减少.

结论:

对于自身抑制,Ca2+反应和基质关联的CaMKII架构可能起源于神经分泌.
在哺乳动物中,CaMKII互动体专门用于突触信号传递,并与α异型的出现有关.
进化分析提供了关于CaMKII在神经元过程中的功能多样化的见解.

关键词:

在Ca2+信号传输中.达利结构比较 DALI结构比较 FrustratoEvo能量丧的挫折感在内突变的突变发生.在RefSeq转录组中.ePISA 联系能源公司

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