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Novel auxin probes on auxin receptors and signal transduction

关于生长素受体和信号转导的新型生长素探针

基本信息

批准号：
18510197
负责人：
HAYASHI Ken-ichiro
金额：
$ 1.52万
依托单位：
Okayama University of Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18510197/
关键词：
auxin Plant hormone TIR1 receptor Molecular probe Terfestatin A F-box protein inhibitor 受容体シロイヌナズナ光標識

项目摘要

The regulation of gene expression by the hormone auxin is a crucial mechanism in plant development. Arabidopsis F-box protein TIR1 is a receptor for auxin and recent structural work has revealed the molecular mechanism of auxin perception. TIR1 is the substrate receptor of the ubiquitin-ligase complex SCF^<TIR1>. However, the detailed relations between signaling and physiological response are still unclear. We have developed two types of auxin probes to study auxin responses by chemical biological approach.1 : Novel synthetic auxin agonists and antagonists. These probes are specific to TIR1-mediated events in Arabidopsis and their mode of action in binding to TIR1 is confirmed by X-ray crystallographic analysis. Further we demonstrate the utility of these probes for the analysis of TIR1-mediated auxin signaling in the moss P. patens. Our work not only provides a new useful tool for plant chemical biology but also demonstrates the first example of a specific small molecule inhibitor of F-box protein-substrate recruitment.2: Novel auxin probes derived from natural products. Terfestatin A (TrfA), a novel auxin signaling inhibitor, was identified in a screen of Streptomyces sp. F40 extracts for inhibition of the expression of an auxin-inducible gene. However, the mode of action of TrfA has not been elucidated. To identify the active core structure, twenty-five derivatives of TrfA were synthesized and their inhibitory activities against auxin-inducible gene expression were evaluated. The structure-activity relationships revealed the essential active core structure of TrfA, 3-butoxy-4-methylbiphenyl-2, 6-diol, which will lead to the design of biotin-tagged active TrfA.

生长素对基因表达的调控是植物发育的重要机制。拟南芥F-box蛋白TIR 1是生长素的受体，最近的结构研究揭示了生长素感受的分子机制。TIR 1是泛素-连接酶复合物SCF α的底物受体<TIR1>。然而，信号传导和生理反应之间的详细关系仍然不清楚。我们已经开发了两种类型的生长素探针来研究生长素反应的化学生物学方法。1：新的合成生长素激动剂和拮抗剂。这些探针是特定的TIR 1介导的事件在拟南芥和他们的行动模式结合TIR 1的X-射线晶体学分析证实。此外，我们证明了这些探针的效用，在藓类P. patens的TIR 1介导的生长素信号的分析。我们的工作不仅为植物化学生物学提供了一个新的有用工具，而且还展示了第一个F-box蛋白质底物募集的特定小分子抑制剂的例子。2：来自天然产物的新型生长素探针。TerfestatinA（TrfA）是一种新型的生长素信号抑制剂，通过对链霉菌F40提取物的筛选，发现它能抑制生长素诱导基因的表达。然而，TrfA的作用方式尚未阐明。为了鉴定活性核心结构，合成了25个TrfA衍生物，并评价了它们对生长素诱导的基因表达的抑制活性。构效关系分析揭示了TrfA的活性核心结构3-丁氧基-4-甲基联苯-2，6-二醇，为设计生物素标记的活性TrfA奠定了基础。