PDBsum entry 3c6n

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protein ligands Protein-protein interface(s) links
Signaling protein PDB id
Protein chains
57 a.a. *
567 a.a. *
Waters ×177
* Residue conservation analysis
PDB id:
Name: Signaling protein
Title: Small molecule agonists and antagonists of f-box protein- substrate interactions in auxin perception and signaling
Structure: Skp1-like protein 1a. Chain: a. Synonym: skp1-like 1, ufo-binding protein 1. Engineered: yes. Transport inhibitor response 1. Chain: b. Synonym: f-box/lrr-repeat protein 1. Engineered: yes
Source: Arabidopsis thaliana. Thale cress. Organism_taxid: 3702. Gene: skp1a, ask1, skp1, uip1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: tir1, fbl1, wei1.
2.60Å     R-factor:   0.190     R-free:   0.281
Authors: X.Tan,N.Zheng,K.Hayashi
Key ref:
K.Hayashi et al. (2008). Small-molecule agonists and antagonists of F-box protein-substrate interactions in auxin perception and signaling. Proc Natl Acad Sci U S A, 105, 5632-5637. PubMed id: 18391211 DOI: 10.1073/pnas.0711146105
04-Feb-08     Release date:   22-Apr-08    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q39255  (SKP1A_ARATH) -  SKP1-like protein 1A
160 a.a.
57 a.a.
Protein chain
Pfam   ArchSchema ?
594 a.a.
567 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     plasma membrane   8 terms 
  Biological process     viral reproduction   27 terms 
  Biochemical function     protein binding     5 terms  


DOI no: 10.1073/pnas.0711146105 Proc Natl Acad Sci U S A 105:5632-5637 (2008)
PubMed id: 18391211  
Small-molecule agonists and antagonists of F-box protein-substrate interactions in auxin perception and signaling.
K.Hayashi, X.Tan, N.Zheng, T.Hatate, Y.Kimura, S.Kepinski, H.Nozaki.
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.
  Selected figure(s)  
Figure 5.
Crystal structure and molecular docking analysis of TIR1–probe complexes. (A and B) Crystal structure of TIR1–probe complexes. TIR1 is shown as silver ribbon. Probes 3, 4, and 8 are shown as blue, yellow, and green, respectively. IAA7 degron peptide (pink, surface-filled model) and IAA (red) were superimposed on the coordinates in the crystal structure of the TIR1-IAA-IAA7 complex. (C) Molecular docking of TIR1 probe. Predicted binding conformers of 3 (blue) and 4 (yellow) to TIR1 auxin-binding site. Fifty possible binding conformers were predicted by the program AutoDock. Ten representative conformers were shown based on rmsd values to the coordinates of IAA moiety in 3 and 4 in crystal structure.
Figure 6.
The TIR1/AFB specific probe 8 blocks auxin responses of moss P. patens. (A) Effects of 8 on NAA-induced elongation of P. patens gametophores. The juvenile gametophore was incubated for 60 h with chemicals (2 μM NAA and/or 20 μM 8). Arrows indicate the elongation zone in response to NAA. (Scale bar, 10 mm.) (B) Effects of 8 and NAA on the development of chloronemata. Chloronema cells were cultured on a BCDATG medium for 10 days in the presence of 0.5 μM NAA and/or 10 μM 8. Arrows indicate caulonemata.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21288713 D.M.Duda, D.C.Scott, M.F.Calabrese, E.S.Zimmerman, N.Zheng, and B.A.Schulman (2011).
Structural regulation of cullin-RING ubiquitin ligase complexes.
  Curr Opin Struct Biol, 21, 257-264.  
21252298 R.Pelagio-Flores, R.Ortíz-Castro, A.Méndez-Bravo, L.Macías-Rodríguez, and J.López-Bucio (2011).
Serotonin, a Tryptophan-Derived Signal Conserved in Plants and Animals, Regulates Root System Architecture Probably Acting as a Natural Auxin Inhibitor in Arabidopsis thaliana.
  Plant Cell Physiol, 52, 490-508.  
21370976 Z.Hua, and R.D.Vierstra (2011).
The cullin-RING ubiquitin-protein ligases.
  Annu Rev Plant Biol, 62, 299-334.  
20888232 B.De Rybel, V.Vassileva, B.Parizot, M.Demeulenaere, W.Grunewald, D.Audenaert, J.Van Campenhout, P.Overvoorde, L.Jansen, S.Vanneste, B.Möller, M.Wilson, T.Holman, G.Van Isterdael, G.Brunoud, M.Vuylsteke, T.Vernoux, L.De Veylder, D.Inzé, D.Weijers, M.J.Bennett, and T.Beeckman (2010).
A novel aux/IAA28 signaling cascade activates GATA23-dependent specification of lateral root founder cell identity.
  Curr Biol, 20, 1697-1706.  
21149713 D.H.Keuskamp, S.Pollmann, L.A.Voesenek, A.J.Peeters, and R.Pierik (2010).
Auxin transport through PIN-FORMED 3 (PIN3) controls shade avoidance and fitness during competition.
  Proc Natl Acad Sci U S A, 107, 22740-22744.  
20505777 G.F.Hao, and G.F.Yang (2010).
The role of Phe82 and Phe351 in auxin-induced substrate perception by TIR1 ubiquitin ligase: a novel insight from molecular dynamics simulations.
  PLoS One, 5, e10742.  
20851666 G.R.Hicks, and N.V.Raikhel (2010).
Advances in dissecting endomembrane trafficking with small molecules.
  Curr Opin Plant Biol, 13, 706-713.  
20488896 K.Hayashi, K.Horie, Y.Hiwatashi, H.Kawaide, S.Yamaguchi, A.Hanada, T.Nakashima, M.Nakajima, L.N.Mander, H.Yamane, M.Hasebe, and H.Nozaki (2010).
Endogenous diterpenes derived from ent-kaurene, a common gibberellin precursor, regulate protonema differentiation of the moss Physcomitrella patens.
  Plant Physiol, 153, 1085-1097.  
  20504967 L.I.Calderon-Villalobos, X.Tan, N.Zheng, and M.Estelle (2010).
Auxin perception--structural insights.
  Cold Spring Harb Perspect Biol, 2, a005546.  
19825020 P.McCourt, and D.Desveaux (2010).
Plant chemical genetics.
  New Phytol, 185, 15-26.  
20036182 R.Tóth, and R.A.van der Hoorn (2010).
Emerging principles in plant chemical genetics.
  Trends Plant Sci, 15, 81-88.  
20192743 S.B.Powles, and Q.Yu (2010).
Evolution in action: plants resistant to herbicides.
  Annu Rev Plant Biol, 61, 317-347.  
19605414 A.Nakamura, S.Fujioka, S.Takatsuto, M.Tsujimoto, H.Kitano, S.Yoshida, T.Asami, and T.Nakano (2009).
Involvement of C-22-hydroxylated brassinosteroids in auxin-induced lamina joint bending in rice.
  Plant Cell Physiol, 50, 1627-1635.  
19553990 A.Santner, and M.Estelle (2009).
Recent advances and emerging trends in plant hormone signalling.
  Nature, 459, 1071-1078.  
19309458 H.Yang, and A.S.Murphy (2009).
Functional expression and characterization of Arabidopsis ABCB, AUX 1 and PIN auxin transporters in Schizosaccharomyces pombe.
  Plant J, 59, 179-191.  
19493348 I.A.Paponov, W.Teale, D.Lang, M.Paponov, R.Reski, S.A.Rensing, and K.Palme (2009).
The evolution of nuclear auxin signalling.
  BMC Evol Biol, 9, 126.  
19424292 R.D.Vierstra (2009).
The ubiquitin-26S proteasome system at the nexus of plant biology.
  Nat Rev Mol Cell Biol, 10, 385-397.  
18708574 A.K.Spartz, and W.M.Gray (2008).
Plant hormone receptors: new perceptions.
  Genes Dev, 22, 2139-2148.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.