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| {{STRUCTURE_3c6p| PDB=3c6p | SCENE= }} | | {{STRUCTURE_3c6p| PDB=3c6p | SCENE= }} |
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| '''Small molecule agonists and antagonists of F-box protein-substrate interactions in auxin perception and signaling'''
| | ===Small molecule agonists and antagonists of F-box protein-substrate interactions in auxin perception and signaling=== |
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| ==Overview==
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| 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. | | The line below this paragraph, {{ABSTRACT_PUBMED_18391211}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 18391211 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_18391211}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Ubiquitin ligase]] | | [[Category: Ubiquitin ligase]] |
| [[Category: Ubl conjugation pathway]] | | [[Category: Ubl conjugation pathway]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Apr 24 09:52:24 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 00:16:35 2008'' |
