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对人类ATE1异型及其与Arg-tRNA_Arg的相互作用进行结构分析

Rahul Naga¹, Sayan Poddar², Arghyadeep Bhattacharjee^1,3

¹Department of Biotechnology, National Institute of Technology, Durgapur, West Bengal, India.

Journal of biomolecular structure & dynamics

|July 28, 2023

概括

这项研究揭示了人类Arginyltransferase 1 (hATE1) 异型之间的结构差异,影响蛋白质功能和基质特异性. 这些发现对于理解细胞过程和疾病中的化非常重要.

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:

翻译后蛋白质化通过影响蛋白质稳定性,功能和宏分子相互作用来调节真核细胞过程.
酶Arginyltransferase (ATE1) 和它的点对于调节正常和疾病状态的细胞功能至关重要.
缺乏关于人类ATE1 (hATE1) 异型的详细结构信息,这阻碍了对其作用的充分理解.

研究的目的:

预测人类ATE1 (hATE1) 酶及其四种异型的整体结构.
为了研究hATE1异型的结构-功能关系.
探索结构变异和非同义单核酸多态 (nsSNP) 对hATE1功能的影响.

主要方法:

通过计算建模了四种hATE1异型的3D结构.
在hATE1异型和Arg-tRNAArg之间进行了分子对接.
进行了分子动力学 (MD) 模拟和根平均方位波动 (RMSF) 分析.
挖掘了非同义单核酸多态 (nsSNP) 来评估它们的影响.

主要成果:

所有的hATE1异型表现出两个不同的域:一个紧的和一个灵活的.
在hATE1-1/X4和hATE1-2/5异型之间注意到了结构上的相似之处.
活性点在位置上保持不变,但在残留量上有所不同,这表明基质特异性各异.
识别了有害的nsSNP,包括与癌症相关的,可能会影响hATE1的结构和功能.

结论:

这项研究提供了对哺乳动物ATE1异型的第一个结构洞察力,突出了它们的差异.
hATE1异型之间的结构变异可能会导致不同的基质特异性和细胞作用.
已识别的NSSNP为了解疾病机制和制定治疗策略提供了潜在的目标.

关键词:

在ATE1中,ATE1是ATE1.甲基转移酶是一种甲基转移酶.有害的nsSNP可以使用.人类ATE1异型.人类ATE1结构

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