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3c6o

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Revision as of 18:14, 8 February 2016

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

Structural highlights

3c6o is a 2 chain structure with sequence from Arath. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3c6n, 3c6p
Gene:	SKP1A, ASK1, SKP1, UIP1 (ARATH), TIR1, FBL1, WEI1 (ARATH)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[SKP1A_ARATH] Involved in ubiquitination and subsequent proteasomal degradation of target proteins. Together with CUL1, RBX1 and a F-box protein, it forms a SCF E3 ubiquitin ligase complex. The functional specificity of this complex depends of the type of F-box protein. In the SCF complex, it serves as an adapter that links the F-box protein to CUL1. SCF(UFO) is required for vegetative and floral organ development as well as for male gametogenesis. SCF(TIR1) is involved in auxin signaling pathway. SCF(COI1) regulates responses to jasmonates. SCF(EID1) and SCF(AFR) are implicated in phytochrome A light signaling. SCF(ADO1), SCF(ADO2), SCF(ADO3) are related to the circadian clock. SCF(ORE9) seems to be involved in senescence. SCF(EBF1/EBF2) may regulate ethylene signaling. Plays a role during embryogenesis and early postembryonic development, especially during cell elongation and division. Contributes to the correct chromosome segregation during tetrad formation.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] [TIR1_ARATH] Auxin receptor that mediates Aux/IAA proteins proteasomal degradation and auxin-regulated transcription. The SCF(TIR1) E3 ubiquitin ligase complex is involved in auxin-mediated signaling pathway that regulate root and hypocotyl growth, lateral root formation, cell elongation, and gravitropism. Appears to allow pericycle cells to overcome G2 arrest prior to lateral root development. Plays a role in ethylene signaling in roots. Confers sensitivity to the virulent bacterial pathogen P.syringae.^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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^[15]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Zhao D, Yang M, Solava J, Ma H. The ASK1 gene regulates development and interacts with the UFO gene to control floral organ identity in Arabidopsis. Dev Genet. 1999 Sep;25(3):209-23. PMID:10528262 doi:<209::AID-DVG4>3.0.CO;2-O 10.1002/(SICI)1520-6408(1999)25:3<209::AID-DVG4>3.0.CO;2-O
↑ Gray WM, del Pozo JC, Walker L, Hobbie L, Risseeuw E, Banks T, Crosby WL, Yang M, Ma H, Estelle M. Identification of an SCF ubiquitin-ligase complex required for auxin response in Arabidopsis thaliana. Genes Dev. 1999 Jul 1;13(13):1678-91. PMID:10398681
↑ Yang M, Hu Y, Lodhi M, McCombie WR, Ma H. The Arabidopsis SKP1-LIKE1 gene is essential for male meiosis and may control homologue separation. Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11416-21. PMID:10500191
↑ Zhao D, Yu Q, Chen M, Ma H. The ASK1 gene regulates B function gene expression in cooperation with UFO and LEAFY in Arabidopsis. Development. 2001 Jul;128(14):2735-46. PMID:11526079
↑ Zhao D, Ni W, Feng B, Han T, Petrasek MG, Ma H. Members of the Arabidopsis-SKP1-like gene family exhibit a variety of expression patterns and may play diverse roles in Arabidopsis. Plant Physiol. 2003 Sep;133(1):203-17. PMID:12970487
↑ Liu F, Ni W, Griffith ME, Huang Z, Chang C, Peng W, Ma H, Xie D. The ASK1 and ASK2 genes are essential for Arabidopsis early development. Plant Cell. 2004 Jan;16(1):5-20. Epub 2003 Dec 19. PMID:14688296 doi:10.1105/tpc.017772
↑ Ruegger M, Dewey E, Gray WM, Hobbie L, Turner J, Estelle M. The TIR1 protein of Arabidopsis functions in auxin response and is related to human SKP2 and yeast grr1p. Genes Dev. 1998 Jan 15;12(2):198-207. PMID:9436980
↑ Gray WM, del Pozo JC, Walker L, Hobbie L, Risseeuw E, Banks T, Crosby WL, Yang M, Ma H, Estelle M. Identification of an SCF ubiquitin-ligase complex required for auxin response in Arabidopsis thaliana. Genes Dev. 1999 Jul 1;13(13):1678-91. PMID:10398681
↑ Alonso JM, Stepanova AN, Solano R, Wisman E, Ferrari S, Ausubel FM, Ecker JR. Five components of the ethylene-response pathway identified in a screen for weak ethylene-insensitive mutants in Arabidopsis. Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2992-7. Epub 2003 Feb 26. PMID:12606727 doi:http://dx.doi.org/10.1073/pnas.0438070100
↑ Dharmasiri N, Dharmasiri S, Weijers D, Lechner E, Yamada M, Hobbie L, Ehrismann JS, Jurgens G, Estelle M. Plant development is regulated by a family of auxin receptor F box proteins. Dev Cell. 2005 Jul;9(1):109-19. PMID:15992545 doi:http://dx.doi.org/S1534-5807(05)00184-X
↑ Dharmasiri N, Dharmasiri S, Estelle M. The F-box protein TIR1 is an auxin receptor. Nature. 2005 May 26;435(7041):441-5. PMID:15917797 doi:http://dx.doi.org/nature03543
↑ Kepinski S, Leyser O. The Arabidopsis F-box protein TIR1 is an auxin receptor. Nature. 2005 May 26;435(7041):446-51. PMID:15917798 doi:http://dx.doi.org/10.1038/nature03542
↑ Navarro L, Dunoyer P, Jay F, Arnold B, Dharmasiri N, Estelle M, Voinnet O, Jones JD. A plant miRNA contributes to antibacterial resistance by repressing auxin signaling. Science. 2006 Apr 21;312(5772):436-9. PMID:16627744 doi:http://dx.doi.org/312/5772/436
↑ 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 U S A. 2008 Apr 8;105(14):5632-7. Epub 2008 Apr 7. PMID:18391211
↑ 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 U S A. 2008 Apr 8;105(14):5632-7. Epub 2008 Apr 7. PMID:18391211

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3c6o"

@@ Line 2: / Line 2: @@
 <StructureSection load='3c6o' size='340' side='right' caption='[[3c6o]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3c6o]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C6O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3C6O FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3c6o]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Arath Arath]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3C6O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3C6O FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2S2:(2S)-2-(1H-INDOL-3-YL)HEXANOIC+ACID'>2S2</scene>, <scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3c6n|3c6n]], [[3c6p|3c6p]]</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SKP1A, ASK1, SKP1, UIP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=3702 Arabidopsis thaliana]), TIR1, FBL1, WEI1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=3702 Arabidopsis thaliana])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SKP1A, ASK1, SKP1, UIP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=3702 ARATH]), TIR1, FBL1, WEI1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=3702 ARATH])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3c6o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c6o OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3c6o RCSB], [http://www.ebi.ac.uk/pdbsum/3c6o PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3c6o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c6o OCA], [http://pdbe.org/3c6o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3c6o RCSB], [http://www.ebi.ac.uk/pdbsum/3c6o PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 18: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3c6o ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 28: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3c6o" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 35: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Arabidopsis thaliana]]
+[[Category: Arath]]
 [[Category: Tan, X]]
 [[Category: Auxin]]

3c6o

From Proteopedia

Revision as of 18:14, 8 February 2016

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

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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