Subgroup-specific intrinsic disorder profiles of arabidopsis NAC transcription factors: Identification of functional hotspots

Stender, Emil G. P.; O'Shea, Charlotte; Skriver, Karen

doi:10.1080/15592324.2015.1010967

Cited by 12 publications

(14 citation statements)

References 31 publications

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“…This aspect was analyzed for ANAC013 and its close relatives. The disorder pattern of ANAC013 shows similarities with the disorder profiles of ANAC016 and ANAC017 (22). These three membrane-bound NAC transcription factors, which are functionally related by mediating oxidative stress signaling (20,25,26), belong to the same sub-group of the NAC family (27).…”

Section: Contribution Of Specific Anac013mentioning

confidence: 76%

“…In this study, we defined the SLiM (DE)X(1,2)(YF)X(1,4)(DE)L for transcription factor binding to RCD1. The functional importance of this SLiM is supported by its conservation in IDRs with low degrees of sequence similarities (22) and by its in vivo role for DREB2A⅐RCD1 interactions (18). A high risk of false-positives exists for motif identification (38), and not all of the regions shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…They share the MEME sequence motif E(KE)(ED)(DEM)(YF)(IL)E(MI)(ND)DL, encompassing the RCD1-interacting core of ANAC013 and coinciding with a MoRF in all three proteins. All three proteins also have a dip in the disorder profile in the same region (22). Based on these characteristics, this region of ANAC016 and ANAC017 is also likely to mediate biochemical interactions with RCD1.…”

Section: Contribution Of Specific Anac013mentioning

confidence: 95%

“…This region contains two pre-dicted MoRFs and two predicted ␣-helical regions. Interestingly, the MEME motif E(KE)(ED)(DEM)(YF)(IL)E(MI)(ND) DL(LM), present in a small sub-group of NAC proteins (22), coincides with one of the predicted MoRFs and ␣-helices. In this study, the ANAC013 TRD was truncated further from both the N-and C-terminal ends and analyzed for its ability to interact with the RST domain of RCD1 in yeast (Fig.…”

Section: Identification Of the Rcd1-binding Region In Anac013-mentioning

confidence: 99%

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Structures and Short Linear Motif of Disordered Transcription Factor Regions Provide Clues to the Interactome of the Cellular Hub Protein Radical-induced Cell Death1

O'Shea¹,

Staby²,

Bendsen

et al. 2017

Journal of Biological Chemistry

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145

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Intrinsically disordered protein regions (IDRs) lack a well defined three-dimensional structure but often facilitate key protein functions. Some interactions between IDRs and folded protein domains rely on short linear motifs (SLiMs). These motifs are challenging to identify, but once found they can point to larger networks of interactions, such as with proteins that serve as hubs for essential cellular functions. The stress-associated plant protein radical-induced cell death1 (RCD1) is one such hub, interacting with many transcription factors via their flexible IDRs. To identify the SLiM bound by RCD1, we analyzed the IDRs in three protein partners, DREB2A (dehydration-responsive element-binding protein 2A), ANAC013, and ANAC046, considering parameters such as disorder, context, charges, and pI. Using a combined bioinformatics and experimental approach, we have identified the bipartite RCD1-binding SLiM as (DE)X(1,2)(YF)X(1,4)(DE)L, with essential contributions from conserved aromatic, acidic, and leucine residues. Detailed thermodynamic analysis revealed both favorable and unfavorable contributions from the IDRs surrounding the SLiM to the interactions with RCD1, and the SLiM affinities ranged from low nanomolar to 50 times higher K values. Specifically, although the SLiM was surrounded by IDRs, individual intrinsic α-helix propensities varied as shown by CD spectroscopy. NMR spectroscopy further demonstrated that DREB2A underwent coupled folding and binding with α-helix formation upon interaction with RCD1, whereas peptides from ANAC013 and ANAC046 formed different structures or were fuzzy in the complexes. These findings allow us to present a model of the stress-associated RCD1-transcription factor interactome and to contribute to the emerging understanding of the interactions between folded hubs and their intrinsically disordered partners.

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Section: Contribution Of Specific Anac013mentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Contribution Of Specific Anac013mentioning

confidence: 95%

Section: Identification Of the Rcd1-binding Region In Anac013-mentioning

confidence: 99%

See 2 more Smart Citations

Structures and Short Linear Motif of Disordered Transcription Factor Regions Provide Clues to the Interactome of the Cellular Hub Protein Radical-induced Cell Death1

O'Shea¹,

Staby²,

Bendsen

et al. 2017

Journal of Biological Chemistry

Self Cite

145

View full text Add to dashboard Cite

show abstract

“…This example underscores how the dynamics and structure of the flanking regions of a SLiM may be even more important than the SLiM itself. For the plant TFs dehydration response element binding proteins 2A (DREB2A) and ANAC013, which both use the [DE]X [1,2][YF]X [1,4][DE] SLiM for binding to the cellular hub protein Radical Induced Cell Death1 (Bugge et al, 2018), disordered regions surrounding the binding motif exert positive and negative allosteric effects on binding, respectively (O'Shea et al, 2017) ( Figure 1G and Table 1), possibly reflected in the function-related conservation of the disorder-order profiles for the NAC transcription factors (Stender et al, 2015). These effects could also be explained by the ensemble allosteric model as derived for GR.…”

Section: Regulation By Dynamic Allosterymentioning

confidence: 99%

Interactions by Disorder – A Matter of Context

Bugge

Brakti

Fernandes

et al. 2020

Front. Mol. Biosci.

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143

127

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Living organisms depend on timely and organized interactions between proteins linked in interactomes of high complexity. The recent increased precision by which protein interactions can be studied, and the enclosure of intrinsic structural disorder, suggest that it is time to zoom out and embrace protein interactions beyond the most central points of physical encounter. The present paper discusses protein-protein interactions in the view of structural disorder with an emphasis on flanking regions and contexts of disorder-based interactions. Context constitutes an overarching concept being of physicochemical, biomolecular, and physiological nature, but it also includes the immediate molecular context of the interaction. For intrinsically disordered proteins, which often function by exploiting short linear motifs, context contributes in highly regulatory and decisive manners and constitute a yet largely unrecognized source of interaction potential in a multitude of biological processes. Through selected examples, this review emphasizes how multivalency, charges and charge clusters, hydrophobic patches, dynamics, energetic frustration, and ensemble redistribution of flanking regions or disordered contexts are emerging as important contributors to allosteric regulation, positive and negative cooperativity, feedback regulation and negative selection in binding. The review emphasizes that understanding context, and in particular the role the molecular disordered context and flanking regions take on in protein interactions, constitute an untapped well of energetic modulation potential, also of relevance to drug discovery and development.

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IDDomainSpotter: Compositional bias reveals domains in long disordered protein regions—Insights from transcription factors

et al. 2019

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Protein domains constitute regions of distinct structural properties and molecular functions that are retained when removed from the rest of the protein. However, due to the lack of tertiary structure, the identification of domains has been largely neglected for long (>50 residues) intrinsically disordered regions. Here we present a sequence‐based approach to assess and visualize domain organization in long intrinsically disordered regions based on compositional sequence biases. An online tool to find putative intrinsically disordered domains (IDDomainSpotter) in any protein sequence or sequence alignment using any particular sequence trait is available at http://www.bio.ku.dk/sbinlab/IDDomainSpotter. Using this tool, we have identified a putative domain enriched in hydrophilic and disorder‐promoting residues (Pro, Ser, and Thr) and depleted in positive charges (Arg and Lys) bordering the folded DNA‐binding domains of several transcription factors (p53, GCR, NAC46, MYB28, and MYB29). This domain, from two different MYB transcription factors, was characterized biophysically to determine its properties. Our analyses show the domain to be extended, dynamic and highly disordered. It connects the DNA‐binding domain to other disordered domains and is present and conserved in several transcription factors from different families and domains of life. This example illustrates the potential of IDDomainSpotter to predict, from sequence alone, putative domains of functional interest in otherwise uncharacterized disordered proteins.

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Subgroup-specific intrinsic disorder profiles of arabidopsis NAC transcription factors: Identification of functional hotspots

Cited by 12 publications

References 31 publications

Structures and Short Linear Motif of Disordered Transcription Factor Regions Provide Clues to the Interactome of the Cellular Hub Protein Radical-induced Cell Death1

Structures and Short Linear Motif of Disordered Transcription Factor Regions Provide Clues to the Interactome of the Cellular Hub Protein Radical-induced Cell Death1

Interactions by Disorder – A Matter of Context

IDDomainSpotter: Compositional bias reveals domains in long disordered protein regions—Insights from transcription factors

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