3C6O

Small molecule agonists and antagonists of F-box protein-substrate interactions in auxin perception and signaling

3C6O の概要

• エントリーDOI: 10.2210/pdb3c6o/pdb
• 関連するPDBエントリー: 3C6N 3C6P
• 分子名称: SKP1-like protein 1A, TRANSPORT INHIBITOR RESPONSE 1, INOSITOL HEXAKISPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: auxin, ubiquitin ligase, f-box, small molecule, chemical biology, plant physiology, auxin signaling pathway, chromosome partition, cytoskeleton, developmental protein, ethylene signaling pathway, nucleus, ubl conjugation pathway, cell cycle, leucine-rich repeat, plant defense, signaling protein
• 由来する生物種: Arabidopsis thaliana (thale cress); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 85642.81

構造登録者

Tan, X. (登録日: 2008-02-04, 公開日: 2008-04-22, 最終更新日: 2025-05-14)

主引用文献

Hayashi, K.,Tan, X.,Zheng, N.,Hatate, T.,Kimura, Y.,Kepinski, S.,Nozaki, H.
Small-molecule agonists and antagonists of F-box protein-substrate interactions in auxin perception and signaling.
Proc.Natl.Acad.Sci.Usa, 105:5632-5637, 2008

PubMed Abstract: The regulation of gene expression by the hormone auxin is a crucial mechanism in plant development. We have shown that the Arabidopsis F-box protein TIR1 is a receptor for auxin, and our recent structural work has revealed the molecular mechanism of auxin perception. TIR1 is the substrate receptor of the ubiquitin-ligase complex SCF(TIR1). Auxin binding enhances the interaction between TIR1 and its substrates, the Aux/IAA repressors, thereby promoting the ubiquitination and degradation of Aux/IAAs, altering the expression of hundreds of genes. TIR1 is the prototype of a new class of hormone receptor and the first example of an SCF ubiquitin-ligase modulated by a small molecule. Here, we describe the design, synthesis, and characterization of a series of auxin agonists and antagonists. We show these molecules 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 Physcomitrella patens. Our work not only provides a useful tool for plant chemical biology but also demonstrates an example of a specific small-molecule inhibitor of F-box protein-substrate recruitment. Substrate recognition and subsequent ubiquitination by SCF-type ubiquitin ligases are central to many cellular processes in eukaryotes, and ubiquitin-ligase function is affected in several human diseases. Our work supports the idea that it may be possible to design small-molecule agents to modulate ubiquitin-ligase function therapeutically.

PubMed: 18391211
DOI: 10.1073/pnas.0711146105

実験手法

X-RAY DIFFRACTION (2.7 Å)