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作 者:孙夫德 任美娜 赵丽娜 马子祎 鲍宇 SUN Fude;REN Meina;ZHAO Lina;MA Ziyi;BAO Yu(Key Laboratory of Molecular Biophysics,Hebei Province,Institute of Biophysics,School of Sciences,Hebei University of Technology,Tianjin 300401,China)
机构地区:[1]河北工业大学理学院生物物理研究所,河北省分子生物物理重点实验室,天津300401
出 处:《河北工业大学学报》2023年第1期1-12,共12页Journal of Hebei University of Technology
基 金:河北省教育厅重点项目(ZD2020140);国家自然科学基金(32201022)。
摘 要:磷酸化修饰是膜蛋白翻译后修饰的重要类型之一,由蛋白激酶和磷酸酶共同调节而保持一种动态平衡,在正常生命活动乃至肿瘤发生中发挥调控作用。磷酸化修饰诱导膜蛋白结构变化可调节蛋白之间结合活力,而关键磷酸化位点突变可破坏蛋白结合并解除相关信号传导的调节。与其他蛋白不同,膜蛋白需要以质膜为介质发挥功能作用,由于膜组成复杂性和不对称性,磷酸化修饰对膜蛋白的质膜定位以及表面贴附至关重要。膜蛋白磷酸化还调节周围磷脂分子的热力学性质和动力学特性,从而加剧对磷脂双分子层有序度的影响。本文重点阐述了膜蛋白磷酸化的分子特征及调控机制,包括磷酸化位点分布,磷酸化修饰对膜蛋白结构调控以及特异膜环境依赖性;系统总结了膜蛋白磷酸化引发的结构变化在各种生物过程中的功能作用,旨在为膜蛋白磷酸化及相关靶向干预研究提供参考。Phosphorylation modification is one of the main type of post-translational modification of membrane proteins.It is regulated by protein kinases and phosphatases to maintain a dynamic balance and play a role in normal life activities and even tumorigenesis.Phosphorylation induces structural changes in membrane proteins that regulate binding activity between proteins.Due to disease mutations,loss of phosphorylation sites may disrupt protein binding and deregulate signal transduction.Different from other proteins,membrane proteins require the plasma membrane as a medium to function.Because membrane composition is complex and asymmetrical,phosphorylation is crucial for the correct localization of membrane proteins.Phosphorylation of membrane proteins also greatly affects the thermodynamic and dynamics properties of the surrounding phospholipid molecules,which intensifies the influence on the order degree of the phospholipid bilayer.This paper focuses on the molecular characteristics and regulation mechanism of membrane protein phosphorylation,including the distribution of phosphorylation sites,the regulation of membrane protein structure and the dependence of phosphorylation on specific membrane environment.The functional roles of membrane protein phosphorylation induced structural changes in various biological processes were systematically summarized in order to provide theoretical references for a further study of membrane protein phosphorylation and relevant targeted intervention.
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