Structural basis for recognition of diverse transcriptional repressors by the TOPLESS family of corepressors

100

Transcriptional repression involves a class of proteins called corepressors that link transcription factors to chromatin remodeling complexes. In plants such as Arabidopsis thaliana, the most prominent corepressor is TOPLESS (TPL), which plays a key role in hormone signaling and development. Here we present the crystallographic structure of the Arabidopsis TPL N-terminal region comprising the LisH and CTLH (C-terminal to LisH) domains and a newly identified third region, which corresponds to a CRA domain. Comparing the structure of TPL with the mammalian TBL1, which shares a similar domain structure and performs a parallel corepressor function, revealed that the plant TPLs have evolved a new tetramerization interface and unique and highly conserved surface for interaction with repressors. Using site-directed mutagenesis, we validated those surfaces in vitro and in vivo and showed that TPL tetramerization and repressor binding are interdependent. Our results illustrate how evolution used a common set of protein domains to create a diversity of corepressors, achieving similar properties with different molecular solutions.

supporting

confidence: 59%

“…2 A and B) was observed in solution. In the first tetrameric form, also proposed by Ke et al (23) for OsTPR2, but not experimentally validated, the dimers interact through helices α6 and 7. This arrangement creates two symmetric tetramerization interfaces of 600 Å 2 each (tetramerization interface I) ( Fig.…”

Section: Resultsmentioning

confidence: 84%

Structure of the Arabidopsis TOPLESS corepressor provides insight into the evolution of transcriptional repression

Martín-Arevalillo

Nanao

Larrieu

et al. 2017

100

“…S7B), the difference in the sensitivity of repression activity to PB1 mutations may reflect different modes of repression enacted by the different TPL truncations. A recent structure of the N-terminal portion of TPL suggests that this result likely reflects the loss of a second TPL dimerization domain in the N100 fragment (30).…”

Section: Resultsmentioning

confidence: 99%

Functional analysis of molecular interactions in synthetic auxin response circuits

Pierre-Jerome

Moss

Lanctot

et al. 2016

Auxin-regulated transcription pivots on the interaction between the AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) repressor proteins and the AUXIN RESPONSE FACTOR (ARF) transcription factors. Recent structural analyses of ARFs and Aux/IAAs have raised questions about the functional complexes driving auxin transcriptional responses. To parse the nature and significance of ARF-DNA and ARF-Aux/IAA interactions, we analyzed structure-guided variants of synthetic auxin response circuits in the budding yeast Saccharomyces cerevisiae. Our analysis revealed that promoter architecture could specify ARF activity and that ARF19 required dimerization at two distinct domains for full transcriptional activation. In addition, monomeric Aux/IAAs were able to repress ARF activity in both yeast and plants. This systematic, quantitative structure-function analysis identified a minimal complex-comprising a single Aux/IAA repressing a pair of dimerized ARFs-sufficient for auxin-induced transcription.auxin signaling | synthetic circuits | transcription | ARF | PB1

“…Second, JAZ proteins recruit members of the TOPLESS (TPL) class of corepressors either through direct binding of TPL to ethylene-response factor-associated amphiphilic repression (EAR) motifs found at the N terminus of a subset of JAZ proteins or indirectly through the EAR motif-containing NINJA adaptor protein that binds to the central ZIM domain of JAZ proteins (Fig. 1A) (12)(13)(14)(15)(16). TPL proteins in turn recruit repressive histone deacetylases and chromatin remodelers (17,18) to inhibit MYC target gene expression epigenetically.…”

mentioning

confidence: 99%

Structural insights into alternative splicing-mediated desensitization of jasmonate signaling

Zhang

et al. 2017

Self Cite

Jasmonate ZIM-domain (JAZ) transcriptional repressors play a key role in regulating jasmonate (JA) signaling in plants. Below a threshold concentration of jasmonoyl isoleucine (JA-Ile), the active form of JA, the C-terminal Jas motif of JAZ proteins binds MYC transcription factors to repress JA signaling. With increasing JA-Ile concentration, the Jas motif binds to JA-Ile and the COI1 subunit of the SCF COI1 E3 ligase, which mediates ubiquitination and proteasomal degradation of JAZ repressors, resulting in derepression of MYC transcription factors. JA signaling subsequently becomes desensitized, in part by feedback induction of JAZ splice variants that lack the C-terminal Jas motif but include an N-terminal cryptic MYC-interaction domain (CMID). The CMID sequence is dissimilar to the Jas motif and is incapable of recruiting SCF COI1 , allowing CMID-containing JAZ splice variants to accumulate in the presence of JA and to re-repress MYC transcription factors as an integral part of reestablishing signal homeostasis. The mechanism by which the CMID represses MYC transcription factors remains elusive. Here we describe the crystal structure of the MYC3-CMID JAZ10 complex. In contrast to the Jas motif, which forms a single continuous helix when bound to MYC3, the CMID adopts a loop-helix-loop-helix architecture with modular interactions with both the Jas-binding groove and the backside of the Jasinteraction domain of MYC3. This clamp-like interaction allows the CMID to bind MYC3 tightly and block access of MED25 (a subunit of the Mediator coactivator complex) to the MYC3 transcriptional activation domain, shedding light on the enigmatic mechanism by which JAZ splice variants desensitize JA signaling.signaling | plant hormone | plant defense | plant pathogen | plant insect