This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
3c6p
From Proteopedia
Small molecule agonists and antagonists of F-box protein-substrate interactions in auxin perception and signaling
Overview
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.
About this Structure
3C6P is a Protein complex structure of sequences from Arabidopsis thaliana. Full crystallographic information is available from OCA.
Reference
Small-molecule agonists and antagonists of F-box protein-substrate interactions in auxin perception and signaling., Hayashi K, Tan X, Zheng N, Hatate T, Kimura Y, Kepinski S, Nozaki H, Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5632-7. Epub 2008 Apr 7. PMID:18391211 Page seeded by OCA on Thu Apr 24 09:52:24 2008
Categories: Arabidopsis thaliana | Protein complex | Tan, X. | Auxin | Auxin signaling pathway | Cell cycle | Chemical biology | Chromosome partition | Cytoplasm | Cytoskeleton | Developmental protein | Ethylene signaling pathway | F-box | Leucine-rich repeat | Nucleus | Plant defense | Plant physiology | Signaling protein | Small molecule | Ubiquitin ligase | Ubl conjugation pathway
