Self-assembly of the bZIP transcription factor ΔFosB

Zhou Yin, Harikanth Venkannagari, Haley Lynch, Galina Aglyamova, Mukund Bhandari, Mischa Machius, Eric J. Nestler, Alfred J. Robison, Gabby Rudenko

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


ΔFosB is a highly stable transcription factor that accumulates in specific brain regions upon chronic exposure to drugs of abuse, stress, or seizures, and mediates lasting behavioral responses. ΔFosB reportedly heterodimerizes with JunD forming a canonical bZIP leucine zipper coiled coil that clamps onto DNA. However, the striking accumulation of ΔFosB protein in brain upon chronic insult has brought its molecular status into question. Here, we demonstrate through a series of crystal structures that the ΔFosB bZIP domain self-assembles into stable oligomeric assemblies that defy the canonical arrangement. The ΔFosB bZIP domain also self-assembles in solution, and in neuron-like Neuro 2a cells it is trapped into molecular arrangements that are consistent with our structures. Our data suggest that, as ΔFosB accumulates in brain in response to chronic insult, it forms non-canonical assemblies. These species may be at the root of ΔFosB's striking protein stability, and its unique transcriptional and behavioral consequences.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalCurrent Research in Structural Biology
StatePublished - Nov 10 2020


  • Activator protein-1 (AP-1)
  • Basic leucine zipper
  • Neurological disorders
  • Protein accumulation
  • Transcription factor
  • ΔFosB

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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