中国老年保健医学2025，Vol.23Issue(6)：3-7,5.DOI:10.3969/j.issn.1672-2671.2025.06.001
8-oxoGTP作为G蛋白α亚基内源性配体的体外研究
In vitro study of 8-oxoGTP as an endogenous ligand of G protein α subunit
摘要
Abstract
Objective Heterotrimeric G proteins are composed of α,β,and γ subunits,in which the α subunit functions as a molecular switch through GDP/GTP cycling and dynamic association/dissociation with the βγ dimer,thereby precisely regulating downstream signaling.This study aimed to investigate whether 8-oxoGTP can serve as an endogenous ligand of the Gα subunit and thereby influence its signal transduction function,expanding our understanding of G protein-mediated signaling regulation under oxi-dative stress.Methods Molecular docking was employed to predict the binding mode of 8-oxoGTP with Gαi;surface plasmon reso-nance(SPR)was used to compare the binding kinetics and affinities of 8-oxoGTP and GTP with Gαi;in vitro activation assays were conducted to evaluate their effects on Gαi activation.Results Molecular docking revealed that 8-oxoGTP forms more hydrogen bonds and salt bridges with Gαi than GTP,suggesting a more stable interaction.SPR analysis showed that 8-oxoGTP exhibited a markedly higher binding affinity to Gαi than GTP(KD=5.24×10-7 M vs.3.95×10-6 M).Functional assays demonstrated that 8-oxoGTP activated Gαi more effectively than GTP.Conclusion 8-oxoGTP is not only a product of oxidative stress but also acts as a potent endogenous ligand of Gαi,enhancing its activation.These findings suggest that oxidized nucleotides may play important roles in cellu-lar signal transduction and pathological regulation,providing new insights into the molecular mechanisms of oxidative stress-related diseases and potential therapeutic targets.关键词
8-oxoGTP/GTP/G蛋白α亚基/分子对接/表面等离子共振Key words
8-oxoGTP/GTP/G protein α subunit/molecular docking/SPR引用本文复制引用
李瑾,潘佳欣,盛刚,蔡剑平..8-oxoGTP作为G蛋白α亚基内源性配体的体外研究[J].中国老年保健医学,2025,23(6):3-7,5.基金项目
国家重点研发计划(编号:2024YFA1109102),中央高水平医院临床科研业务费(编号:BJ-2023-246) （编号:2024YFA1109102）
