复杂运动情境下AMPK的多位点修饰及其活性调节——基于蛋白质结构生物学的解析  

Multi-Site Modification and Activity Regulation of AMPK in the Complex Context of Exercise—Analysis Based on Protein Structure Biology

作　　者：王静艺 邹勇[1,2] 漆正堂 WANG Jingyi;ZOU Yong;QI Zhengtang(Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education,East China Normal University,Shanghai 200241,China;College of Physical Education and Health,East China Normal University,Shanghai 200241,China)

机构地区：[1]华东师范大学“青少年健康评价与运动干预”教育部重点实验室,上海200241 [2]华东师范大学体育与健康学院,上海200241

出　　处：《体育科学》2023年第4期73-82,共10页China Sport Science

基　　金：“青少年健康评价与运动干预”教育部重点实验室开放课题(40500-23204-542500/006/001)。

摘　　要：腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)以异源三聚体的形式广泛存在于真核生物体内,被认为是细胞的能量感受器和机体的核心代谢调节因子。运动与AMPK的相关研究已持续数十年,研究发现:1)急性运动迅速激活AMPK;2)长期训练提升安静状态AMPK的活性;3)长期训练减弱AMPK对运动的应激反应。这表明AMPK对研究中设置的运动情境很敏感。AMPK的蛋白结构包含多个磷酸化位点,以及泛素化、SUMO化、乙酰化、甲基化和氧化位点,这些位点的共价修饰大部分是可逆和可组合的。通过结构生物学的解析可以预测,AMPK蛋白复合物并非只有简单的激活态与失活态,α-Thr172磷酸化不一定是AMPK酶活性的生物标记。多个位点的翻译后修饰以及变构调节,让AMPK亚基可能组合成不同中间状态,蛋白结构的柔性让AMPK能够以不同活性形态应对复杂的生理情境(包括复杂的运动情境)。未来的研究可以探讨多位点修饰与AMPK活性之间的对应关系,从而进一步解析AMPK对运动的响应机制。AMP-activated protein kinase(AMPK)exists widely in eukaryotes in the form of heterotrimers,and is considered as an energy sensor of cell and a core metabolic regulator of the body.Studies on the relationship between exercise and AMPK have lasted for decades,and found that:1)acute exercise rapidly activates AMPK;2)long-term training improves the activity of AMPK in rest state;3)long-term training attenuates AMPK response to exercise stress.This suggests that AMPK is sensitive to the exercise context set up in the study.The protein structure of AMPK contains multiple phosphorylation sites,as well as ubiquitination,SUMOylation,acetylation,methylation and oxidation sites,most of covalent modifications of these sites are reversible and combinable.The analysis of structural biology can predict that AMPK protein complex is not only a simple“activated state”and“deactivated state”,andα-Thr172 phosphorylation is not necessarily a biomarker of AMPK enzyme activity.Post-translational modification and allosteric regulation at multiple sites enable AMPK subunits to form different intermediate states.The flexibility of the protein structure enables AMPK to respond to complex physiological situations(including complex exercise situations)with different active forms.Future studies can explore the correspondence between multi-site modification and AMPK activity,so as to further analyze the response mechanism of AMPK to exercise.

关 键 词：AMPK 运动 多位点修饰 结构生物学 

分 类 号：G804.2[文化科学—运动人体科学]