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

Proc Natl Acad Sci U S A. 2017 Jul 25;114(30):8107-8112. doi: 10.1073/pnas.1703054114. Epub 2017 Jul 11.

Abstract

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.

Keywords: TOPLESS; auxin signaling; corepressor; crystal structure; tetramerization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Arabidopsis / genetics*
  • Arabidopsis / metabolism
  • Arabidopsis Proteins / genetics*
  • Arabidopsis Proteins / metabolism
  • Co-Repressor Proteins / genetics*
  • Co-Repressor Proteins / metabolism
  • Evolution, Molecular*
  • Gene Expression Regulation, Plant*
  • Hydrophobic and Hydrophilic Interactions
  • Protein Multimerization

Substances

  • Arabidopsis Proteins
  • Co-Repressor Proteins
  • topless protein, Arabidopsis