The Leucine Zipper: A Hypothetical Structure Common to a New Class of DNA Binding Proteins

TLDR

A 30‑amino‑acid segment of the enhancer‑binding protein C/EBP shows sequence similarity to Myc, and similar leucine‑rich motifs are also found in Fos, Jun, and yeast GCN4, indicating a common structural feature among these proteins. The authors propose that these leucine‑rich segments adopt α‑helical conformations whose side chains interdigitate between two helices, enabling dimerization. By modeling the sequences on an idealized α‑helix, they observed a periodic repetition of leucine residues every seventh position across eight turns, suggesting a zipper‑like arrangement. They coined this arrangement the “leucine zipper,” proposing it as a defining feature of a new class of DNA‑binding proteins.

Abstract

A 30-amino-acid segment of C/EBP, a newly discovered enhancer binding protein, shares notable sequence similarity with a segment of the cellular Myc transforming protein. Display of these respective amino acid sequences on an idealized α helix revealed a periodic repetition of leucine residues at every seventh position over a distance covering eight helical turns. The periodic array of at least four leucines was also noted in the sequences of the Fos and Jun transforming proteins, as well as that of the yeast gene regulatory protein, GCN4. The polypeptide segments containing these periodic arrays of leucine residues are proposed to exist in an α-helical conformation, and the leucine side chains extending from one α helix interdigitate with those displayed from a similar α helix of a second polypeptide, facilitating dimerization. This hypothetical structure is referred to as the "leucine zipper," and it may represent a characteristic property of a new category of DNA binding proteins.