构象景观适应使Src家族激酶的过程磷酸化成为可能，这一成果由圣犹达儿童研究医院
利用核磁共振波谱，课题组人员在Src构象系中发现了一个介于活性和非活性之间的瞬态中间态。这种中间状态促进了三磷酸腺苷水解后二磷酸腺苷的快速释放，确保了有效的催化转化。中间状态的缺失消除了Src、Lck和Hck的过程磷酸化，损害了功能。这些发现表明，Src家族激酶的构象集合已经进化为包含一种瞬时状态，这支持了它们对过程底物磷酸化的能力。
研究人员表示，激酶的过程磷酸化使信号中心的快速多位点修饰成为可能，在时间敏感的细胞事件中整合信号。为了获得处理能力，在底物解离之前必须进行多次催化循环，这使得快速的周转率至关重要。Src家族激酶对多位点底物进行持续磷酸化。
附：英文原文
Title: Conformational landscape adaptations enable processive phosphorylation by Src family kinases
Author: Yixin Cui, Rustam Ali, Mary Clay, Paolo Rossi, Aizhuo Liu, Darong Yang, Nancy R. Gough, Terrence Geiger, Charalampos G. Kalodimos
Issue&Volume: 2025-12-18
Abstract: Processive phosphorylation by kinases enables the rapid multisite modification of signaling hubs, serving to integrate signals during time-sensitive cellular events. To achieve processivity, multiple catalytic cycles must occur before substrate dissociation, making rapid turnover rates essential. Src family kinases processively phosphorylate multisite substrates. Using nuclear magnetic resonance spectroscopy, we identified a transient intermediate state within the Src conformational ensemble, positioned between its active and inactive states. This intermediate state facilitates the rapid release of adenosine diphosphate following adenosine triphosphate hydrolysis, ensuring efficient catalytic turnover. Depletion of the intermediate state abrogated processive phosphorylation by Src, Lck, and Hck, impairing function. These findings reveal that the conformational ensemble of Src family kinases has evolved to incorporate a transient state that underpins their capacity for processive substrate phosphorylation.
DOI: adw8310
Source: https://www.science.org/doi/10.1126/science.adw8310