The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
Accession:
Functional site class:
Phytohormone-dependent SCF-LRR-binding degrons
Functional site description:
Several plant-specific degrons mediate phytohormone-dependent binding of regulatory proteins to F-box proteins that function as substrate recognition subunits of the SCF (Skp1-Cul1-Rbx1-Fbox protein) E3 ubiquitin ligase, which targets its substrates for subsequent proteasomal degradation. An auxin-dependent degron motif is present in Aux/IAA proteins and mediates binding of these transcriptional repressors to TIR1/AFB F-box proteins. Similarly, a jasmonate-dependent degron motif is present in JAZ proteins and mediates binding of these transcriptional repressors to the COI1 F-box protein. Binding of these degrons to the leucine-rich repeats (LRRs) of their respective F-box proteins is hormone-dependent, as binding of a hormone molecule to the F-box protein results in the formation of a composite binding site for the substrate degron sequence. The resulting tripartite complex allows high-affinity binding of the substrate protein to the F-box protein.
ELMs with same func. site: DEG_SCF_COI1_1  DEG_SCF_TIR1_1 
ELM Description:
Binding of the degron to the auxin-bound leucine-rich repeats (LRRs) (SM00370) of TIR1 mainly occurs through hydrophobic interactions mediated by the conserved GWPPV core of the motif (2P1Q) (Tan,2007; Paponov,2009). In addition, the regions flanking this central part also contribute to binding and show some preference for specific residues. Variability outside the core might reflect different specificities of the different degrons for the different auxin-responsive F-box proteins, including TIR1, AFB1-3 and GRH1 in Arabidopsis. The degron adopts a coiled conformation, with the core motif inserted in a hydrophobic surface pocket on TIR1 and covering the auxin molecule bound at the bottom of this pocket. The tryptophan and second proline provide hydrophobic interactions with TIR1 and auxin. These two residues are locked in a proper conformation by the first proline, which also forms hydrophobic interactions with TIR1. The invariant glycine provides the flexibility that is required for the peptide to make a sharp turn at the exit of the TIR1 pocket, so that it can make additional contacts with TIR1 using its upstream flanking region. This includes the first position, which is undefined but frequently contains a glutamine. Following the two prolines is an additional residue, mostly valine, that makes hydrophobic contacts with TIR1. The region downstream of this position frequently contains basic residues, predominantly arginine. The invariant arginine in position 12 might stabilize the peptide through intramolecular interactions. The basic residues are often but not always preceded by an aromatic residue in position 11. The auxin molecule inserted in the cavity at the degron-TIR1 interface stabilizes the interaction between Aux/IAA and TIR1 and increases the affinity by interacting with both binding partners. Some Aux/IAA proteins appear to lack a functional TIR1-binding degron motif (IAA20/IAA30) or have only parts of it conserved (IAA29), which might indicate an altered functionality.
Pattern: .[VLIA][VLI]GWPP[VLI]...R.
Pattern Probability: 1.336e-09
Present in taxon: Viridiplantae
Interaction Domain:
LRR (SM00370) Leucine-rich repeats, outliers (Stochiometry: 1 : 1)
PDB Structure: 2P1Q
o See 24 Instances for DEG_SCF_TIR1_1
o Abstract
Phytohormones are a diverse set of endogenous chemicals that control many different aspects of plant development and growth. Some well-studied plant hormones include auxins, ethylene, gibberellins, jasmonates and abscisic acid. Their activity depends on hormone synthesis, transport, conjugation to other substances, and degradation, as well as extensive cross talk between the different hormones (Garay-Arroyo,2012).
The auxin family of plant hormones, with indole-3-acetic acid (IAA) as the most important member, plays a key role in plant development and growth by acting as a signal for cell division, elongation and differentiation. This hormone regulates a wide variety of processes, including embryogenesis, root formation, apical dominance and tropic responses to light and gravity (Mockaitis,2008, Hayashi,2012). Local auxin abundance is determined by the coordinated control of regulatory pathways involved in the metabolism and transport of auxin. Responses to auxin are mediated by a variety of signalling mechanisms that control the expression of specific sets of genes or trigger transcription-independent responses. Genes transcriptionally activated by auxin include GH3 genes involved in synthesis of inactive IAA-amino acid conjugates, the Small Auxin-Up RNA (SAUR) genes of unknown function, and the Aux/IAA genes. Important mediators of the transcriptional response to auxin are the auxin response factor (ARF) transcription factors that directly bind to the promoters of auxin-responsive genes to regulate their expression. The auxin-responsiveness of the ARFs depends on the Aux/IAA proteins, transcriptional repressors that heterodimerize with ARF proteins, thereby inactivating ARF activity and blocking transcription of auxin-responsive genes. In the presence of auxin, the Aux/IAA repressors are targeted for ubiquitin-dependent proteasomal degradation by the SCF (Skp1-Cul1-Rbx1-Fbox protein) E3 ubiquitin ligase. The auxin-dependent degradation of the Aux/IAAs relieves inhibition of ARF activity and results in expression of auxin-responsive genes. As these genes also include the Aux/IAA-encoding genes, this mechanism provides a negative feedback loop for control of auxin signalling (Mockaitis,2008, Hayashi,2012).
Degradation of the Aux/IAA proteins by the SCF complex depends on the Transport Inhibitor Response 1 (TIR1) and Auxin signalling F-Box (AFB) proteins that function as auxin receptors and substrate recognition subunits of the SCF. The Aux/IAAs are recruited to the SCF by a TIR1/AFB F-box protein, subsequently ubiquitylated by the SCF, and thereby marked for degradation by the proteasome. Binding to the F-box subunit is mediated by the auxin-dependent SCF-TIR1-binding degron motif. Auxin promotes an increase of Aux/IAA degradation by enhancing the interaction between the motif and TIR1/AFB (Parry,2006, Calderon-Villalobos,2010). The components of this transcriptional auxin response are conserved in plants, although some Aux/IAA proteins appear to lack a functional TIR1-binding degron motif (Dreher,2006, Paponov,2009).
The oxylipin jasmonic acid (JA) and its metabolites constitute a family of plant hormones collectively referred to as jasmonates. Production of the major bioactive isoform of the hormone, N-[(3R,7S)-(+)-7-iso-Jasmonoyl]-(S)-isoleucine (JA-Ile), requires conjugation of the JA prohormone to isoleucine (Fonseca,2009). Jasmonates play an important role in normal plant development and growth processes, including root growth, including inhibition of root growth and seed germination and stimulation of senescence. In addition, they mediate defensive responses to biotic and abiotic stress signals such as pathogenic infection, wounding and UV irradiation (Wasternack,2007). Jasmonate-induced responses depend on signalling mechanisms that control the expression of specific sets of genes. An important mediator of the transcriptional response to jasmonates is the transcription factor MYC2/RAP1, which directly binds to the promoters of JA-responsive genes. Genes regulated by MYC2 include wound-responsive genes and genes involved in redox signalling (Dombrecht,2007). The JA-responsiveness of MYC2 and the related transcription factors MYC3 and MYC4 depends on the JAZ/TIFY proteins that function as transcriptional repressors and inhibit positive regulation of gene expression by MYC2. In the absence of bioactive jasmonates, the JAZ proteins bind to MYC2 through their C-terminal region. The inhibitory function of JAZ proteins depends on their ZIM domain that binds to the adaptor protein NINJA, which in turn recruits the general corepressor TOPLESS (Pauwels,2011, Kombrink,2012). In the presence of active JA, the JAZ proteins are targeted for ubiquitin-dependent proteasomal degradation by the SCF (Skp1-Cul1-Rbx1-Fbox protein) E3 ubiquitin ligase. The JA-dependent degradation of the JAZ proteins relieves inhibition of MYC2 activity and results in expression of JA-responsive genes. As these genes also include the JAZ-encoding genes, this mechanism provides a negative feedback loop for control of jasmonate signalling (Fonseca,2009).
Degradation of the JAZ proteins by the SCF complex depends on the Coronatine-insensitive protein 1 (COI1), which functions as a JA receptor and substrate recognition subunit of the SCF. The JAZ proteins are recruited to the SCF by the COI1 F-box protein, subsequently ubiquitylated by the SCF, and thereby marked for degradation by the proteasome. Binding to the F-box subunit is mediated by the JA-dependent SCF-COI1-binding degron motif located in the Jas domain, which mediates binding to MYC2. JA-Ile promotes an increase of JAZ degradation by enhancing the interaction between the motif and COI1 (Gfeller,2010, Kombrink,2012). The components of this transcriptional JA response are conserved in higher plants, although some JAZ proteins appear to lack a functional COI1-binding degron motif (Pauwels,2011, Shyu,2012).
o 6 selected references:

o 7 GO-Terms:

o 24 Instances for DEG_SCF_TIR1_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
Q9C966 IAA15
IAA15_ARATH
70 82 TNDQLVGWPPVATARKTVRR U 1 Arabidopsis thaliana (Thale cress)
P49680 IAA6
IAA6_PEA
55 67 KKNQVVGWPPVCSYRKKNMN TP 1 Pisum sativum (Pea)
Q38822 IAA3
IAA3_ARATH
64 76 RKAQIVGWPPVRSYRKNNIQ TP 2 Arabidopsis thaliana (Thale cress)
1 
Q38830 IAA12
IAA12_ARATH
69 81 RSSQVVGWPPIGLHRMNSLV TP 3 Arabidopsis thaliana (Thale cress)
1 
P49677 IAA1
IAA1_ARATH
55 67 AKTQIVGWPPVRSNRKNNNN TP 3 Arabidopsis thaliana (Thale cress)
1 
P93830 IAA17
IAA17_ARATH
82 94 AKAQVVGWPPVRSYRKNVMV TP 3 Arabidopsis thaliana (Thale cress)
1 
Q38825 IAA7
IAA7_ARATH
82 94 AKAQVVGWPPVRNYRKNMMT TP 5 Arabidopsis thaliana (Thale cress)
1 
Q9XFM0 IAA28
IAA28_ARATH
48 60 EVAPVVGWPPVRSSRRNLTA TP 2 Arabidopsis thaliana (Thale cress)
1 
Q38828 IAA10
IAA10_ARATH
93 105 TRQVAVGWPPLRTYRINSLV U 1 Arabidopsis thaliana (Thale cress)
Q38831 IAA13
IAA13_ARATH
76 88 SSSQVVGWPPIGSHRMNSLV U 1 Arabidopsis thaliana (Thale cress)
Q38829 IAA11
IAA11_ARATH
88 100 TSGQVVGWPPIRTYRMNSMV U 1 Arabidopsis thaliana (Thale cress)
Q9ZSY8 IAA27
IAA27_ARATH
143 155 SKAQVVGWPPIRSFRKNSMA U 1 Arabidopsis thaliana (Thale cress)
Q38826 IAA8
IAA8_ARATH
165 177 AKAQVVGWPPIRSYRKNTMA U 1 Arabidopsis thaliana (Thale cress)
Q38824 IAA6
IAA6_ARATH
70 82 VKSQAVGWPPVCSYRRKKNN U 1 Arabidopsis thaliana (Thale cress)
P33078 IAA5
IAA5_ARATH
53 65 KKSQVVGWPPVCSYRRKNSL U 1 Arabidopsis thaliana (Thale cress)
O24409 IAA19
IAA19_ARATH
70 82 AKSQVVGWPPVCSYRKKNSC U 1 Arabidopsis thaliana (Thale cress)
Q38832 IAA14
IAA14_ARATH
76 88 AKAQVVGWPPVRNYRKNVMA U 1 Arabidopsis thaliana (Thale cress)
O24407 IAA16
IAA16_ARATH
70 82 AKAQVVGWPPVRSFRKNVMS U 1 Arabidopsis thaliana (Thale cress)
Q38827 IAA9
IAA9_ARATH
183 195 AKAQIVGWPPVRSYRKNTLA U 1 Arabidopsis thaliana (Thale cress)
P33077 IAA4
IAA4_ARATH
62 74 PKAQIVGWPPVRSYRKNNVQ U 1 Arabidopsis thaliana (Thale cress)
P49679 IAA4/5
IAA4_PEA
70 82 AKAKIVGWPPIRSYRKNSLH U 1 Pisum sativum (Pea)
P49678 IAA2
IAA2_ARATH
60 72 TKTQIVGWPPVRSSRKNNNS U 1 Arabidopsis thaliana (Thale cress)
O24408 IAA18
IAA18_ARATH
96 108 APGPVVGWPPVRSFRKNLAS U 1 Arabidopsis thaliana (Thale cress)
Q8LAL2 IAA26
IAA26_ARATH
103 115 APGPVVGWPPVRSFRKNLAS U 1 Arabidopsis thaliana (Thale cress)
Please cite: ELM 2016-data update and new functionality of the eukaryotic linear motif resource. (PMID:26615199)

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