bZIP

bZIP refers to a family of transcription factors characterized by a basic region that binds DNA and a leucine zipper that mediates dimerization. The proteins in this family are found across eukaryotes and participate in diverse cellular processes including development, metabolism, and stress responses.

Structure and mechanism: The basic region is rich in lysine and arginine and contacts DNA in the major groove of target motifs. The leucine zipper consists of a heptad-repeat of leucine residues that forms a coiled-coil, enabling homo- or heterodimerization. Dimerization expands binding diversity and can alter target sequence specificity and transcriptional output. The bZIP domain is often accompanied by additional regulatory regions that control activity via phosphorylation, redox state, or interactions with coactivators.

Functions and examples: In yeast, GCN4 is a well-studied bZIP factor that activates amino acid biosynthesis genes. In mammals, CREB and the AP-1 family (comprising c-Fos and c-Jun) are prototypical bZIP transcription factors. Plant genomes encode large bZIP families that regulate responses to light and stress and ABA signaling. The activity of bZIP factors integrates signaling pathways to control gene expression programs.

Regulation and significance: bZIP proteins can form various dimer combinations, influencing DNA-binding specificity and transcriptional output. Post-translational modifications and subcellular localization further regulate activity. Due to central roles in development, metabolism, and disease, bZIP factors are common targets of research and potential therapeutic interventions.