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Molecular mechanism of trehalose 6-phosphate inhibition of the plant metabolic sensor kinase SnRK1
Science Advances ( IF 11.7 ) Pub Date : 2024-05-17 , DOI: 10.1126/sciadv.adn0895
Jantana Blanford 1 , Zhiyang Zhai 1 , Marcel D Baer 2 , Gongrui Guo 1 , Hui Liu 1 , Qun Liu 1 , Simone Raugei 2 , John Shanklin 1
Affiliation  

SUCROSE-NON-FERMENTING1-RELATED PROTEIN KINASE1 (SnRK1), a central plant metabolic sensor kinase, phosphorylates its target proteins, triggering a global shift from anabolism to catabolism. Molecular modeling revealed that upon binding of KIN10 to GEMINIVIRUS REP-INTERACTING KINASE1 (GRIK1), KIN10’s activation T-loop reorients into GRIK1’s active site, enabling its phosphorylation and activation. Trehalose 6-phosphate (T6P) is a proxy for cellular sugar status and a potent inhibitor of SnRK1. T6P binds to KIN10, a SnRK1 catalytic subunit, weakening its affinity for GRIK1. Here, we investigate the molecular details of T6P inhibition of KIN10. Molecular dynamics simulations and in vitro phosphorylation assays identified and validated the T6P binding site on KIN10. Under high-sugar conditions, T6P binds to KIN10, blocking the reorientation of its activation loop and preventing its phosphorylation and activation by GRIK1. Under these conditions, SnRK1 maintains only basal activity levels, minimizing phosphorylation of its target proteins, thereby facilitating a general shift from catabolism to anabolism.

中文翻译:


海藻糖6-磷酸抑制植物代谢传感器激酶SnRK1的分子机制



蔗糖非发酵 1 相关蛋白激酶 1 (SnRK1) 是一种中心植物代谢传感器激酶,可磷酸化其靶蛋白,引发从合成代谢到分解代谢的整体转变。分子模型显示,KIN10 与 GEMINIVIRUS REP-INTERACTING KINASE1 (GRIK1) 结合后,KIN10 的激活 T 环重新定向到 GRIK1 的活性位点,从而使其磷酸化和激活。海藻糖 6-磷酸 (T6P) 是细胞糖状态的代表,也是 SnRK1 的有效抑制剂。 T6P 与 SnRK1 催化亚基 KIN10 结合,削弱其与 GRIK1 的亲和力。在这里,我们研究了 T6P 抑制 KIN10 的分子细节。分子动力学模拟和体外磷酸化测定鉴定并验证了 KIN10 上的 T6P 结合位点。在高糖条件下,T6P 与 KIN10 结合,阻断其激活环的重新定向,并阻止其被 GRIK1 磷酸化和激活。在这些条件下,SnRK1 仅维持基础活性水平,最大限度地减少其靶蛋白的磷酸化,从而促进从分解代谢到合成代谢的总体转变。
更新日期:2024-05-17
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