Design of a bZip transcription factor with homo/heterodimer-induced DNA-binding preference

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Vivian Pogenberg - , European Molecular Biology Laboratory (EMBL) Hamburg, German Electron Synchrotron (DESY) (Author)
  • Larissa Consani Textor - , European Molecular Biology Laboratory (EMBL) Hamburg (Author)
  • Laurent Vanhille - , Marseille-Luminy Immunology Center (CIML) (Author)
  • Simon J Holton - , European Molecular Biology Laboratory (EMBL) Hamburg (Author)
  • Michael H Sieweke - , Marseille-Luminy Immunology Center (CIML), Aix-Marseille Université, INSERM - Institut national de la santé et de la recherche médicale, French National Centre for Scientific Research (CNRS), Max Delbrück Center for Molecular Medicine (MDC) (Author)
  • Matthias Wilmanns - , European Molecular Biology Laboratory (EMBL) Hamburg (Author)

Abstract

The ability of basic leucine zipper transcription factors for homo- or heterodimerization provides a paradigm for combinatorial control of eukaryotic gene expression. It has been unclear, however, how facultative dimerization results in alternative DNA-binding repertoires on distinct regulatory elements. To unravel the molecular basis of such coupled preferences, we determined two high-resolution structures of the transcription factor MafB as a homodimer and as a heterodimer with c-Fos bound to variants of the Maf-recognition element. The structures revealed several unexpected and dimer-specific coiled-coil-heptad interactions. Based on these findings, we have engineered two MafB mutants with opposite dimerization preferences. One of them showed a strong preference for MafB/c-Fos heterodimerization and enabled selection of heterodimer-favoring over homodimer-specific Maf-recognition element variants. Our data provide a concept for transcription factor design to selectively activate dimer-specific pathways and binding repertoires.

Details

Original languageEnglish
Pages (from-to)466-77
Number of pages12
JournalStructure
Volume22
Issue number3
Publication statusPublished - 4 Mar 2014
Peer-reviewedYes
Externally publishedYes

External IDs

Scopus 84896694912

Keywords

Keywords

  • Amino Acid Sequence, Animals, Basic-Leucine Zipper Transcription Factors/chemistry, Binding Sites, DNA/metabolism, MafB Transcription Factor/chemistry, Mice, Models, Molecular, Molecular Sequence Data, Mutation, Protein Conformation, Protein Engineering/methods, Protein Multimerization, Proto-Oncogene Proteins c-fos/chemistry