Intrinsic and extrinsic regulators of Aux/IAA protein degradation dynamics

Abstract

The plant hormone auxin acts through regulated degradation of Auxin/INDOLE-3-ACETIC ACID INDUCIBLE (Aux/IAA) proteins to regulate transcriptional events. In this review, we examine the composition and function of each Aux/IAA structural motif. We then focus on recent characterization of Aux/IAA N-terminal disordered regions, formation of secondary structure within these disordered regions, and post-translational modifications that affect Aux/IAA function and stability. We propose how structural variations between Aux/IAA family members may be tuned for differential transcriptional repression and degradation dynamics.

Auxin perception: a lens through which to examine degron interactions

Protein interfaces, conformations, and post translational modifications fundamentally modulate precise decision-making mechanisms in signaling networks. Further, protein stability and regulated degradation play essential roles in cellular processes such as metabolism and signal transduction Plants incorporate fast protein degradation mechanisms into nearly all studied signal transduction pathways, with ~5% of the Arabidopsis genome dedicated to encoding plant protein degradation machinery [1]. More specifically, the auxin signal transduction pathway (see Glossary) is one of the best studied plant pathways requiring rapid protein degradation for hormone response.

The plant hormone auxin triggers multiple rapid plant physiological and transcriptional responses. A repression-derepression paradigm governs auxin transcriptional responses. The Auxin/INDOLE-3-ACETIC ACID (Aux/IAA) family of transcriptional repressors modulates the activity of the AUXIN RESPONSIVE FACTOR (ARF) family of transcription factors. In the presence of auxin, Aux/IAA repressor proteins are degraded through the activity of the ubiquitin ligase protein E3 SKP1-CULLIN1-F-BOX (SCF) complex with F-BOX protein TRANSPORT INHIBITOR RESPONSE1 (TIR1) and its homologs AUXIN SIGNALING F-BOX1–5 (AFB1–5). Auxin acts as a molecular glue, assembling the Aux/IAA degradation Short Linear Motif (SLiM - Degron) into the TIR1/AFB binding site within the Leucine Reach Repeat (LRR) motif (Figures 1 and 2). This auxin-driven association of the Aux/IAA repressor with an SCF^TIR/AFB promotes Aux/IAA polyubiquitylation, resulting in Aux/IAA degradation via the proteasome. This removal of the Aux/IAA repressor permits ARF activity and results in transcription of genes that will enact auxin responses (reviewed in [2–4]).

Figure 1:

Auxin signaling pathway. When auxin levels are low, Aux/IAAs and the TPL corepressor together repress transcription. ARFs bind to DNA at the C-terminal DNA binding domain (DBD) and its transcriptional activity is repressed through interaction between the ARF N-terminal PB1 domain and the Aux/IAA PB1 domain. TPL recruits histone deacetylases and also interacts with Mediator to prevent ARF transcriptional output. Under elevated auxin levels, the hormone promotes SCF^TIR/AFB-Auxin-Aux/IAA association and stimulates Aux/IAA polyubiquitylation and degradation via proteasome. Once free from TPL and Aux/IAA repression, the mediator and ARF transcriptional machinery recruits RNA polymerase II and gene expression is initiated, inducing auxin-responsive transcription.

Figure 2:

Aux/IAA-Auxin-TIR/AFB co-receptor assembly. A) A model of TIR1, auxin (IAA), and Aux/IAA7 interaction. Shown is a surface model of TIR1 (gray) with auxin (green) promoting interaction with Aux/IAA7 (blue ribbon diagram. Highlighted in orange are the Aux/IAA residues that make the degron, KR dipeptide motif, and PB1 domain contact points that interact with TIR1 residues in red (S201 and R220 interact with the PB1 domain and D448 with KR). The model was constructed using the available structures (TIR1, PDB ID: 2P1Q [12] and IAA PB1domain, PDB ID: 2M1M [17]). Degron-receptor docking was adjusted as originally characterized [12]; PB1 and KR interactions as described in [20] B) Orthogonal close-up view of the Aux/IAA7 degron peptide (PDB: 2P1Q [12] with auxin (green) at the TIR1 binding pocket (gray with interacting residues in red). Non-covalent interactions occurring within the Aux/IAA peptide, auxin and TIR1 binding pocket are indicated with dashed lines. Hydrogen bonds between arginine and the cis peptidyl-prolyl bond at WP (QVVGWPPVRNYRK), may arrange the degron in a favorable energetic state to maintain WP at cis position for proper TIR1 interaction in the presence of auxin. Images were generated using MolStar [61].

In this review, we describe the structure of Aux/IAA proteins, and then discuss recent insights into the relationship between Aux/IAA protein conformation and structure and roles in auxin co-receptor assembly. We present an integrative view of the mechanisms behind gene transcription repression and auxin-induced protein degradation, discussing recent proteomics, protein structure, NMR, and co-receptor binding kinetic data.

Aux/IAA protein domains and motifs

Aux/IAA proteins are characterized by two motifs and a folded Phox and Bem1 (PB1) domain (Figure 2). The first motif, known as DI, contains conserved LxLxL residues that are an Ethylene-responsive element binding factor-associated Amphiphilic Repression (EAR) motif. EAR motifs interact with the transcriptional co-repressor TOPLESS (TPL) [5]. Mutation of the LxLxL motif in IAA 7, 17, or 19 depletes their ability to inhibit auxin-regulated transcription [6]. Although Aux/IAA-mediated recruitment of TPL to repress auxin-regulated transcription has been attributed to its ability to recruit histone deacetylases, recent studies suggest that TPL recruitment by Aux/IAA proteins also prevents full assembly of the Mediator complex [7] (Figure 1). This mechanism of allowing a partially assembled transcriptional complex at a transcriptional start site may explain the rapid release of transcription repression upon Aux/IAA degradation, similar to promoter proximal pausing [8].

Motif DII (DII) contributes to Aux/IAA degradation [9]. DII contains the SLiM degron, characterized by VGWPP[V/I][R/G]XXR amino acid sequence that adopts a folded configuration to compactly interact with the hydrophobic LRR domain pocket in TIR/AFB coreceptor in the presence of auxin (Figure 2) [10–12]. Degron consensus sequence variants directly impact Aux/IAA stability interaction with different TIR/AFB co-receptors [10,13]. Non-canonical Aux/IAA proteins, for example, have divergent degron sequences or lack the DII motif entirely, inducing partial or total insensitivity to auxin due to an inability to bind TIR/AFB [9]. Additionally, gain-of-function mutations in the conserved degron leads to auxin insensitivity in several plants, disrupting the assembly of the auxin co-receptor complex [14]. Differences in Aux/IAA degradation rates are primarily driven by variation of the degron sequence, conferring each Aux/IAA with distinct degradation dynamics (reviewed at [15]).

The Aux/IAA carboxy-terminal PB1 domain facilitates Aux/IAA-ARF and Aux/IAA-Aux/IAA interactions (Figure 1). Aux/IAA and ARF PB1 domains have conserved lysines and aspartic acids on opposite faces of the domain that enable multimerization amongst Aux/IAA and ARF PB1 domains [16,17]; however, the existence of multimerized ARF and Aux/IAA proteins bound to chromatin has not been documented. The PB1-mediated interprotein interactions in Aux/IAA-mediated transcriptional repression seem to be specific and varies depending on the Aux/IAA family member. Mutation on either positive or negative faces of IAA16 fully disrupts transcriptional repression activity [16], partially disrupts IAA19 and 17 repression activity [18], and has little effect on IAA17 repression activity [19]. Thus, the stochiometry requirement for Aux/IAA repression of ARF activity is not fully resolved. Further, the impact of intrinsic (amino-acid composition) and extrinsic (post-translational modifications) Aux/IAA and ARF PB1 features that regulate interactions amongst these families is still being deciphered.

Aux/IAA intrinsic disorder allows tuned auxin co-receptor formation

Aux/IAA regions containing DI and DII motifs are intrinsically disordered regions (IDRs), lack well-defined tertiary structures, and dynamically adopt heterogeneous conformers [20]. Molecular plasticity allows IDRs to adapt structural conformation for interaction with other proteins, which can be mediated through conserved SLiMs and/or context binding to the binding partner [21–23]. SLiMs are characterized by conserved compact-short stretches (6–12 amino acids) of adjacent amino acids within IDRs. These modules provide precise recognition and interaction with structured partner proteins [21–24]. Degrons, such as those found in Aux/IAAs, are a subclass of SLiMs, acting as signaling agents for protein degradation. The Aux/IAA degron fits into the auxin-TIR/AFB binding pocket. IDR binding to structured proteins is often governed by the chemical composition of amino acids, in which chemical features, but perhaps not specific amino acids, are conserved. In some cases, these participate in interaction based on multiple and distinct contexts, forming multiple transient interactive clusters with its interactor. In other cases, these IDR regions are unable to directly bind the interactor but occur in the vicinity of the SLiM to adjust the SLiM at the binding site. The classification and characterization of interactive and modeling clusters in IDRs are complex and broad, involving diverse physicochemical contexts, such as presence of folded domains or allosteric binding [21,23,25]. Context and motif binding can synergistically affect these protein interactions.

In the last 20 years of auxin research, reports on Aux/IAA stability focused on the degron-mediated assembly of auxin co-receptors and on sequence variation of the conserved degron [10,26–29]. However, the influence of regions outside the degron on protein degradation have been observed, and the importance of context-related interactions of other regions of the Aux/IAA IDR is arising as an important modulator of protein stability, particularly the Lys-Arg (KR) dipeptide motif (Figure 2A) [9,20], and additional regions proximal to the degron [13,20,30,31].

There are 29 Arabidopsis Aux/IAA proteins and the dynamic basis of intrinsic disorder and secondary structure properties of family members are poorly characterized [32]. Of these, only the IAA17 N-terminus has had its secondary structure experimentally solved by NMR [33]. To gain perspective on potential secondary structures in Aux/IAA family N-termini, we predicted secondary structures [34] and compared them to the characterized IAA17 N-terminus [33] (Figure 3). The structural predications suggest the EAR motif assumes a helix structure, matching structural observations of EAR-TPL interactions [33,35,36]. The region between the KR dipeptide and degron are predicted to display intermediate disorder, with variable predicted secondary structures (Figure 3). The core degron, GWPPVR, is consistently predicted to be unstructured, whereas the region immediately N-terminal to the degron is typically predicted to form a β-sheet (IAA18, 26 and 31 are exceptions). Immediately C-terminal to the degron, distinct sets of Aux/IAA proteins have differing predicted secondary structure; IAA3, 7, 10, 11, 12, 13, 14, 15, 18, 26 and 28 are predicated to be coiled C-terminal to the degron, whereas IAA9, 16, 17 and 29 are predicted to adopt a β-sheet C-terminal to the degron. IAA1, 2, 3, 4, 5, 6, 8, and 19 are predicted to remain unstructured in this region. These differing predicted elements in the N-termini of the Aux/IAA proteins, which participate in auxin co-receptor formation more than previously appreciated, may provide clues toward understanding the differing interaction dynamics of their participation in auxin perception.

Figure 3.

Arabidopsis Aux/IAA proteins display conserved and distinct features. Shown at the top is the Aux/IAA17 N-terminal amino-acid sequence, color scored according to conservation among Aux/IAA proteins in Arabidopsis thaliana [62]. Below are N-terminal portions of all Arabidopsis Aux/IAA proteins, aligned by the degron [63]. IAA17 secondary structure defined by NMR [33], predicted by Alphafold [64] and by the consensus predictor NPS@ [34] (using the models MLRC [65], DPM [66], DSC [67], GOR1 [68] and GOR3 [69]). Additional Aux/IAA protein secondary structural tendencies were defined using the consensus predictor NPS@. Unstructured regions are shown in red, yellow arrows depict predicted beta-sheets, and black coils represent predicted alpha-helixes. Conserved degrons are highlighted in purple, KR in light gray and EAR in dark gray. Post-translational modifications from various proteomics analyses are highlighted, with ubiquitylation represented as orange circles [20,41,42] and phosphorylation as blue diamonds [51].

Aux/IAA conformational plasticity

IDR conformation plasticity can be essential for interactions with structured binding partners. However, some SLiM-flanking regions contain stabilizing ordered conformations, such as β-sheets, α-helixes, or irregular secondary structures to facilitate binding and module recognition with interaction partners (reviewed in [37]). Three distinct regions surrounding the degron motif of IAA17 tend to form β-secondary structures (β1=A79–Q82, β2=V89–R93 and β3 = V96–Q101; Figures 3 and 4) [33]. The residues forming β1 and β2 are moderately conserved within the Arabidopsis Aux/IAA family, whereas residues of β3 are not conserved (Figure 3). Our in silico analysis of IAA17 predicts β1 and β3, but not β2 (Figure 3). During TIR1 binding, the IAA7 degron peptide (⁸⁹VRNYRK⁹⁴) is extended and stabilized by hydrogen bonds to adjacent degron residues and to TIR1 residues within the crystal structure (2P1Q - [12], Figure 2B), similar to that found by NMR for the IAA17 degron [33]. The NMR analysis of IAA17-TIR1 interaction further found IAA17 contact points with TIR1 distal to the degron [33].

Figure 4.

Aux/IAA17 fragment half-lives from the yeast synthetic auxin degradation system [13]. Fragment sequences are represented with secondary structures identified by NMR [33]; yellow arrows correspond to beta-sheets. The degron is highlighted in a purple box and the KR dipeptide motif in a gray box.

In the synthetic recapitulated auxin signal transduction yeast system [13], the IAA17⁸²⁻⁹³ fragment containing the core degron and a single β-secondary structure, displays an 80-minute half-life (Figure 4). In contrast, inclusion of the C-terminal region (IAA17³¹⁻⁹⁵) results in a 40-minute half-life. Further, expansion to include all the three β-secondary structures surrounding the degron (IAA17⁷⁷⁻¹¹¹) results in a 20-minute half-life, which most closely approximates the full-length DII peptide (IAA17³¹⁻¹¹¹) half-life of 10 minutes. IAA1, 3, and 28 show the same trend [13], with increased sequence surrounding the core degron resulting in decreased half-lives of these proteins. In the Auxin Inducible Degron system (AID), a synthetic biology tool that uses the auxin signaling system to conditionally induce protein degradation, extending Aux/IAA residues beyond the core degron also alters degradation dynamics [38]. In yeast, the minimal IAA17, the minimal degron required for auxin response consisted of residues 71–114 [39], suggesting the core ‘degron’ (Figure 2) is insufficient to capture the required interactions between IAA17 and TIR1 for co-receptor formation. Additionally, deletion of nine residues located immediately downstream of the degron in the Sisymbrium orientale IAA2 degron peptide reduces co-receptor complex assembly in the presence of auxin [31], suggesting that the requirement of these residues is broadly conserved. Further studies will be necessary to determine the full impact of secondary structure formation for proper Aux/IAA adjustment into the binding pocket of the TIR/AFB co-receptor.

Aux/IAA – TIR/AFB binding distal from the core degron

Context binding modulation of protein components located far from the SLiM can regulate IDRs/IDPs and their interactions with partner proteins. These secondary, distal, recognition sites can cause allosteric regulation of the protein interaction, in which this binding induces IDR conformational changes and/or its interaction partner to alter association (reviewed in [23]).

Aux/IAA regions distantly located from the core degron, which has the best-defined association with auxin and the TIR/AFB coreceptors, seem to act as allosteric regulators of coreceptor interaction, both at the auxin binding site and elsewhere in the protein (Figure 2A). The length and flexibility of its N-terminus enables electrostatic interaction between the conserved KR dipeptide of IAA7 with a cluster of residues on the TIR1 surface, centered on D481 [20]. Additionally, auxin-independent interactions between IAA7 and TIR1 were found between the IAA7 PB1 domain and another cluster within the leucine-rich repeat domain of TIR1, centered on R220 and S201 [20]. Thermodynamic studies of IDR-containing protein ligands show that long non-conserved regions flaking binding motifs often stabilize the secondary structure of the binding motif, increase protein-receptor interactions, and decrease conformational entropy of the folded binding site of the binding partner [25]. In the case of the auxin co-receptor system, the long and non-conserved IDR located to either side of the core degron, bounded by KR and PB1 side interactions, may induce energetic stabilization for proper binding of the core degron [20]. Further, NMR analysis of the interaction between IAA17 and TIR1 identifies binding interfaces across several portions of the IAA17 IDR, including the DI/EAR motif [33]. The impact of these interactions on modulating degron conformations and auxin binding affinity is still unknown, but we hypothesize that they may act to tune the affinity and specificity among the different TIR/AFB co-receptors and members of Aux/IAA family.

Aux/IAA post-translational modifications regulate stability and co-receptor formation

Post-translational modifications alter protein physicochemical properties to affect protein function, stability, folding, and compartmentalization [40]. Aux/IAAs are marked by multiple types of post-translational modifications; some of these modifications have well-described effects on Aux/IAA stability and function whereas the relevance of other modifications is still being discovered.

Ubiquitylation

Degradation of Aux/IAA proteins, regulated by their polyubiquitylation and targeting to the 26S proteasome, is essential for auxin-mediated transcriptional regulation (Figure 1). Although lysines are the most favorable ubiquitylation sites, alternative acceptors for ubiquitylation can also be used. In vitro ubiquitylation experiments of IAA7, 9, 12, and 13 suggest that certain lysines occupy positions that are more favorably ubiquitylated than others, indicating that structural composition and disposition of interacting interfaces affect the likelihood of ubiquitylation [20,41]. Indeed, proteomic analysis suggests that regions surrounding the IAA degron core and PB1 domain tend to be targeted for ubiquitylation (Figure 3) [42]. However, arginine substitutions for all IAA1 lysine residues only mildly impacts its stability, such that IAA1 lysine variants maintain rapid degradation rates in vivo [43]; this data suggests that alternative residues can be polyubiquitylated in the absence of lysine residues. Thus, whereas specific Aux/IAA sites may be preferable ubiquitylation targets, the affinity between Aux/IAA proteins and SCF^TIR/AFB is what likely drives Aux/IAA ubiquitylation so long as there is a possible acceptor site.

Cis-trans isomerization

Diprolines uniquely undergo cis-trans isomerization, which can act as a molecular switch to affect protein-protein interactions. Trans isomers are energetically favorable and more recurrent in nature. Cis-trans isomerases catalyze the conversion between the two conformers to impact regulation and function of target proteins (reviewed in [44]). In the auxin co-receptor complex, TIR1 exclusively binds the cis Trp-Pro (W-P) isomer of the degron (Figure 2B) [12]. In rice, a cyclophilin-type peptidyl-prolyl cis/trans isomerase called LATERAL ROOTLESS 2 (LRT2) induces the isomerization of the OsIAA11 degron W-P bond to promote its binding to OsTIR1 [45]. In vitro experiments show that OsIAA11and OsIAA13 cis isomerization is positively correlated with LRT2 concentration [46], raising the possibility that LRT2 expression levels may act as a regulatory mechanism for Aux/IAA protein turnover. Further, NMR analysis reveals an unusually high cis/trans ratio (1:1) of the IAA17 W-P bond; the IAA17 cis isomer displays stronger binding energy and slower dissociation with TIR1 in the presence of auxin, compared to trans isomer [33].

Examination of the disposition of the IAA7 degron peptide (⁸²QVVGWPPVRNYRK⁹⁴) within the TIR1 crystal structure in the presence of IAA and NAA (2P1Q, 2P1O [12]) reveals hydrogen bonds between the tryptophan-proline (⁸⁶W-P⁸⁷) and guanidine of arginine (R⁹³) group that may facilitate stabilization of cis positioning of the Aux/IAA peptidyl-prolyl (Figure 2B). The arginine next to the degron (GWPPXXXXR) is present in all canonical Arabidopsis Aux/IAA proteins (Figure 3) and conserved across plant species, indicating functional importance [47]. Further, Aux/IAA and TIR1 interactions are fuzzy at sites distal from the auxin-binding pocket [33]. This primary interaction state may help the formation of electrostatic contacts, favoring natural formation and stabilization of cis isomers. The W-P bond cis isomer locks the degron in the TIR1 binding pocket. [33]. The non-covalent interaction between ⁸⁶W-P⁸⁷ and R⁹³ at IAA7 degron peptide does not occur at the TIR1 binding pocket in the presence of the synthetic auxin 2,4-dichlorophenoxyacetic acid (2,4-D); although the W-P bond is in the cis-conformation during TIR1-degron co-receptor assembly. Formation of these polar contacts is thus not essential for receptor recognition; however, these molecular interactions may explain the faster dissociation rates of 2,4-D compared with the natural auxin IAA (2P1N [10,12]). Overall, the importance of secondary structure interactions in shaping the protein to find its binding site within the Aux/IAA IDR is still unclear, additional elements outside the degron may play an important role in making W-P cis/trans position to regulate protein degradation.

Phosphorylation

Protein phosphorylation introduces negative charge onto otherwise neutral amino acids (Ser, Thr, or Tyr), altering protein structure and interaction. IDRs are particularly prone to phosphorylation [48]. Phosphorylation-mediated changes in protein charge may define conformational shifts; phosphorylation of neutral or negatively-charged amino acid stretches tends to result in chain expansion whereas phosphorylation of positively charged amino acid regions results in chain shrinkage.

Aux/IAA proteins are phosphorylated both in vitro [49,50] and in vivo [51]. Proteomics detects many phosphorylated residues, especially in areas surrounding the degron core (Figure 3). Further, phosphosites on the PB1 domains of IAA 6, 7, 9, 28, and 29 are located close to charged residues that mediate protein oligomerization, suggesting these could regulate Aux/IAA interaction with other Aux/IAA and ARF proteins (for more details on PB1 phosphosites, see [51]). Although treatment with kinase and phosphatase inhibitors does not alter co-receptor formation [52–54], a recent study suggests IAA33 phosphorylation, mediated by MAP KINASE14, increases IAA33 stability [55]. Additionally, the C-terminal portion of TransMembrane Kinases (TMKs) [56] is cleaved and translocated to the nucleus where it stabilizes IAA32 and IAA34 proteins via phosphorylation [57]. Finally, the photoreceptor PhytochromeA (PhyA) can phosphorylate several Aux/IAA proteins, leading to increased IAA protein stability [50,58,59] and interaction between PhyA, PhyB, or CRYPTOCHROME1 (CRY1) with Aux/IAA proteins protects these repressors from degradation by competing with TIR1 for binding to block TIR/AFB co-receptor assembly [58,59]. This contrasting evidence raises questions about the role of phosphorylation in Aux/IAA stability and transcription repression, opening new areas for future research on the understanding of auxin signaling.

Proteolysis regulation mediated by SLiMs and context-based interactions often exhibits complex switching behavior. Post-translational modifications are additional integrative regulatory decision-making components that dynamically facilitate shifts of protein functional states [60]. Most of the impact of these key regulatory modules on Aux/IAA proteins is yet to be explored - we propose that post-translation modifications may be fundamental components to regulate aspects of auxin signaling in plant development and environmental response.

Concluding remarks

Aux/IAAs are small, poorly structured, and ephemeral proteins entrusted to regulate one of the most dynamic and influential gene regulation systems in plants. This dynamic regulation is achieved through two primary Aux/IAA features: rapid degradation and repression of ARF-mediated gene expression. To accomplish these challenging functions in the time frame of an Aux/IAA half-life, these proteins are easily modified, depending on the cellular environment. Despite improvements in the characterization of roles of different Aux/IAA motifs and modifications in regulating gene expression, several aspects that remain unclarified (see Outstanding questions). Advances in auxin research may provide new insights on the behavior and action of protein turnover regulation, gene expression, and hormone crosstalk on different aspects of plant development and environmental adaptation. Additionally, protein structural analyses are opening new possibilities on precise characterization of degron- and context-based interactions. It is exciting to unravel how a simple protein such as the Aux/IAA, in association with a small molecule like auxin and their TIR/AFB co-receptors lead to complex output dynamics based on rapid protein degradation.

Outstanding questions.

Do non-covalent interactions generated by secondary structures surrounding the degron facilitate formation of the W-P bond cis isomer configuration?

How does Aux/IAA phosphorylation status alter co-receptor formation?

What is the function of the secondary EAR motif, found in a subset of Aux/IAA proteins?

In addition to the conserved KR motif within all Aux/IAAs, do other distal interaction sites modulate co-receptor assembly?

How do TIR/AFB orthologs differentially interact with these additional Aux/IAA contact points?

What is the importance of secondary structure within the degron itself for proper binding to the auxin binding site?

Highlights.

Auxin controls many aspects of plant growth and development by regulating the degradation of short-lived Auxin/INDOLE-3-ACETIC ACID INDUCIBLE (Aux/IAA) transcriptional repressors.

Advances in protein structural biology are allowing detailed characterization of the non-globular and intrinsically disordered N-terminal portions of Aux/IAA proteins, revealing how amino-acid composition and post-translational modifications of the N-terminus are essential for regulated proteolysis.

Motif- and context-based interactions of the N-termini of Aux/IAA proteins regulate interactions with TIR1/AFB auxin co-receptors and also with ubiquitin ligase receptors.

Glossary

Auxin Inducible Degron (AID) system

Synthetic biology tool that uses signaling receptor components from the plant auxin signal transduction pathway to study the controlled depletion of proteins in vivo

Auxin signal transduction pathway

Nuclear signaling system regulated by the hormone auxin, involving a tightly regulated-ubiquitin mediated proteolysis of Aux/IAA transcriptional repressor proteins

Degron

Minimal sequence of conserved amino acids to induce degradation in proteins

Intrinsically disordered regions (IDR)

A region of a protein that lacks a fixed three-dimensional configuration. When the entire protein lacks a fixed three-dimensional structure, it is referred to as an intrinsically disordered protein (IDP)

SKP1-CULLIN1-F-BOX (SCF)

As a part of the Ubiquitin Proteasome System, SCF complexes are E3 ubiquitin ligase complexes with multiple components (the Skp1, CULLIN, and F-box) that recruit the E2 ubiquitin conjugating enzyme and recognizes substrate proteins to facilitate their ubiquitylation

Short Linear Motif (SLiM)

Conserved short amino acid sequence that is recognized by protein binding partners; frequently located in intrinsically disordered regions