Molecular mechanism of trehalose 6-phosphate inhibition of the plant metabolic sensor kinase SnRK1

被引：5

作者：

Blanford, Jantana ^{[1
]}

Zhai, Zhiyang ^{[1
]}

Baer, Marcel D. ^{[2
]}

Guo, Gongrui ^{[1
]}

Liu, Hui ^{[1
]}

Liu, Qun ^{[1
]}

Raugei, Simone ^{[2
]}

Shanklin, John ^{[1
]}

机构：

[1] Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA

[2] Pacific Northwest Natl Lab, Phys & Computat Sci Directorate, Richland, WA 99354 USA

来源：

SCIENCE ADVANCES | 2024年 / 10卷 / 20期

关键词：

PROTEIN; ARABIDOPSIS; DYNAMICS; PHOSPHORYLATION; ACTIVATION; EQUILIBRIUM; SIMULATIONS; VALIDATION; REGULATORS; WRINKLED1;

D O I：

10.1126/sciadv.adn0895

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10