6UCM

Transcription factor DeltaFosB bZIP domain self-assembly, type-II crystal

Summary for 6UCM

• Entry DOI: 10.2210/pdb6ucm/pdb
• Related: 6UCI 6UCL
• Descriptor: Protein fosB, 1,2-ETHANEDIOL, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: activator protein-1, basic leucine zipper, bzip, deltafosb fos, jun, transcription factor, dna-binding protein, coiled-coil, transcription
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 3
• Total formula weight: 25214.36

Authors

Yin, Z.,Machius, M.,Rudenko, G. (deposition date: 2019-09-16, release date: 2020-01-15, Last modification date: 2023-10-11)

Primary citation

Yin, Z.,Venkannagari, H.,Lynch, H.,Aglyamova, G.,Bhandari, M.,Machius, M.,Nestler, E.J.,Robison, A.J.,Rudenko, G.
Self-assembly of the bZIP transcription factor Delta FosB.
Curr Res Struct Biol, 2:1-13, 2020

PubMed Abstract: 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.

PubMed: 32542236
DOI: 10.1016/j.crstbi.2019.12.001

Experimental method

X-RAY DIFFRACTION (2.424 Å)