Leucine Zipper


The leucine zipper is a protein–protein interaction domain consisting of amphipathic α helices that dimerize in parallel, either as homodimers or heterodimers, to form a coiled‐coil.

Keywords: dimer; B‐ZIP; heterodimer; electrostatic; amphipathic; DNA binding

Figure 1.

X‐ray structure of the B‐ZIP dimer GCN4 bound to DNA. The DNA is in red, the α helices are in blue. The d or leucine position amino acids are shown in grey. The N‐terminal and C‐terminal parts of the protein are labelled N and C.

Figure 2.

A schematic of the B‐ZIP PAR family member VBP viewed from the side with the amino acids from the VBP leucine zipper shown inside the circles which represent amino acid positions along the two α helices. Amino acids in the e and g position are shown in bold face and the i, i′+5 (g↔e′) interactions are connected by arrows pointing from acidic to basic. The heptad letter designations (a, b, c, d, e, f, g) are shown. The supercoiling of the two helices is not depicted. To the left of the leucine zipper is the basic region of B‐ZIP proteins with the DNA shown. To the right is an end view of a leucine zipper dimer looking from the N‐terminus. The letters on the inside of each ellipse represents the standard nomenclature for the seven amino acids found in unique positions in a coiled‐coil. The ellipses depict the orientations of the amino acid side‐chains relative to the α helix. Amino acids in the a and d positions create a hydrophobic core between the interacting helices. The interaction seen between amino acids in the g and subsequent e′ position seen in X‐ray structures is noted as g↔e′ pairs. Note that because of the 2‐fold symmetry of the dimers, each heptad contains two g↔e′ pairs.

Figure 3.

An end view, looking from the N‐terminus, of the leucine zipper interface with either leucine or isoleucine in the d and d′ positions. The clockwise blue‐green spirals represent α helices. The space‐filling dots represent the volume of the side‐chains. Note that the leucines pack nicely together while the isoleucines overlap, which is not possible physically.

Figure 4.

Double mutant alanine thermodynamic cycle used to determine coupling energy (ΔΔGint) for the interaction of glutamic acid (E) in the g position with arginine (R) in the following e′ position. The ΔΔG values presented are in terms of an individual g↔e′ interaction. The E↔R pair is 1.26 kcal mol−1 more stable than the A↔A pair. The contribution of the individual amino acids to the stability of the leucine zipper was determined by studying proteins containing only glutamic (E↔A) or arginine (A↔R) of the pair. The E↔A pair is 0.11 kcal mol−1 more stable than the A↔A pair. The A↔R pair is 0.67 kcal mol−1 more stable than A↔A. The sum of the individual contributions of E and R to the dimer stability is −0.78 kcal mol−1. The extra −0.46 kcal mol−1 of stability (−1.26−(−0.78)) from the E↔R pair is the coupling energy (ΔΔGint), indicative of the interaction of E with R across the surface of the leucine zipper.

Figure 5.

X‐ray structure showing the Fos/Jun heterodimer with the basic region bound to DNA and the leucine zipper region interacting with another DNA‐binding protein, nuclear factor of T cells (NFAT). Interactions with NFAT occur through conserved amino acids in the b, c and f positions of the Fos/Jun leucine zipper.



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How to Cite close
Krylov, Dmitry, and Vinson, Charles R(Apr 2001) Leucine Zipper. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0003001]