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Publication Abstract from PubMed

DeltaFosB 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. DeltaFosB reportedly heterodimerizes with JunD forming a canonical bZIP leucine zipper coiled coil that clamps onto DNA. However, the striking accumulation of DeltaFosB protein in brain upon chronic insult has brought its molecular status into question. Here, we demonstrate through a series of crystal structures that the DeltaFosB bZIP domain self-assembles into stable oligomeric assemblies that defy the canonical arrangement. The DeltaFosB 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 DeltaFosB accumulates in brain in response to chronic insult, it forms non-canonical assemblies. These species may be at the root of DeltaFosB's striking protein stability, and its unique transcriptional and behavioral consequences.

Self-assembly of the bZIP transcription factor DeltaFosB.,Yin Z, Venkannagari H, Lynch H, Aglyamova G, Bhandari M, Machius M, Nestler EJ, Robison AJ, Rudenko G Curr Res Struct Biol. 2020;2:1-13. doi: 10.1016/j.crstbi.2019.12.001. Epub 2019, Dec 24. PMID:32542236^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.