3c6n

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{{STRUCTURE_3c6n| PDB=3c6n | SCENE= }}
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'''Small molecule agonists and antagonists of F-box protein-substrate interactions in auxin perception and signaling'''
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===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.
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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]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 13:57:29 2008''

Revision as of 10:57, 29 July 2008

Image:3c6n.png

Template:STRUCTURE 3c6n

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

Template:ABSTRACT PUBMED 18391211

About this Structure

3C6N 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

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