A D53 repression motif induces oligomerization of TOPLESS corepressors and promotes assembly of a corepressor-nucleosome complex

Sci Adv. 2017 Jun 2;3(6):e1601217. doi: 10.1126/sciadv.1601217. eCollection 2017 Jun.

Abstract

TOPLESS are tetrameric plant corepressors of the conserved Tup1/Groucho/TLE (transducin-like enhancer of split) family. We show that they interact through their TOPLESS domains (TPDs) with two functionally important ethylene response factor-associated amphiphilic repression (EAR) motifs of the rice strigolactone signaling repressor D53: the universally conserved EAR-3 and the monocot-specific EAR-2. We present the crystal structure of the monocot-specific EAR-2 peptide in complex with the TOPLESS-related protein 2 (TPR2) TPD, in which the EAR-2 motif binds the same TPD groove as jasmonate and auxin signaling repressors but makes additional contacts with a second TPD site to mediate TPD tetramer-tetramer interaction. We validated the functional relevance of the two TPD binding sites in reporter gene assays and in transgenic rice and demonstrate that EAR-2 binding induces TPD oligomerization. Moreover, we demonstrate that the TPD directly binds nucleosomes and the tails of histones H3 and H4. Higher-order assembly of TPD complexes induced by EAR-2 binding markedly stabilizes the nucleosome-TPD interaction. These results establish a new TPD-repressor binding mode that promotes TPD oligomerization and TPD-nucleosome interaction, thus illustrating the initial assembly of a repressor-corepressor-nucleosome complex.

Keywords: D53; Groucho; TOPLESS; corepressor; nucleosome; strigolactone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs*
  • Amino Acid Sequence
  • Co-Repressor Proteins / chemistry*
  • Co-Repressor Proteins / metabolism*
  • Histones / chemistry
  • Histones / metabolism
  • Humans
  • Macromolecular Substances
  • Models, Biological
  • Models, Molecular
  • Mutation
  • Nucleosomes / metabolism*
  • Peptides / chemistry
  • Peptides / metabolism
  • Phenotype
  • Plant Proteins / chemistry
  • Plant Proteins / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Multimerization*
  • Repressor Proteins / chemistry*
  • Repressor Proteins / metabolism*
  • Signal Transduction
  • Structure-Activity Relationship

Substances

  • Co-Repressor Proteins
  • Histones
  • Macromolecular Substances
  • Nucleosomes
  • Peptides
  • Plant Proteins
  • Repressor Proteins