Leucine zipper

They were first described by Landschulz and collaborators in 1988[2] when they found that an enhancer binding protein had a very characteristic 30-amino acid segment and the display of these amino acid sequences on an idealized alpha helix revealed a periodic repetition of leucine residues at every seventh position over a distance covering eight helical turns.

The polypeptide segments containing these periodic arrays of leucine residues were proposed to exist in an alpha-helical conformation and the leucine side chains from one alpha helix interdigitate with those from the alpha helix of a second polypeptide, facilitating dimerization.

[5] Leucine zipper is created by the dimerization of two specific alpha helix monomers bound to DNA.

The ZIP domain is found in the alpha-helix of each monomer, and contains leucines, or leucine-like amino acids.

The alternating three- and four-residue sequence elements constitute heptad repeats in which the amino acids are designated from a’ to g’.

With apolar amino acid residues at either the e or g position, a heterotetramer consisting of 2 different leucine zippers can be generated in-vitro, which implies that the overall hydrophobicity of the interaction surface and van der Waals interaction may alter the organization of coiled coils and play a role in the formation of leucine zipper heterodimer.

[2][4][11] The bZIP heterodimers exist in a variety of eukaryotes and are more common in organisms with higher evolution complexity.

This suggests that, as heterodimers, bZIP transcription factors are able to change their preferences for which location they target in the DNA.

The C-terminal portion of the b-ZIP domain contains an amphipathic leucine zipper region, which mediates homo- and hetero- dimerization.

In cancer cells, NFIL3 associates with Histone deacetylase2 (HDAC2) and represses pro-apoptotic genes such as Tumor necrosis factor ligand superfamily member 10 (TRAIL) and TNF receptor superfamily member 6 (FAS) to prevent apoptosis.

In colon cancer, NFIL3 may also block the recruitment of another type of transcription factors, Proline Acid Rich (PAR) proteins.

Meanwhile, NFIL3 binds to its own promoter to repress its own expression, creating a negative feedback regulation of neuron regeneration.