Leucine Zipper

Abstract

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.

close

References

Carr CM and Kim PS (1993) A spring‐loaded mechanism for the conformational change of influenza hemagglutinin. Cell 73(4): 823–832.

Crick F (1953) The packing of Ãhelices: simple coiled‐coils. Acta Crystallographica 6: 689–697.

Ellenberger TE, Brandl CJ, Struhl K and Harrison SC (1992) The GCN4 basic region leucine zipper binds DNA as a dimer of uninterrupted alpha helices: crystal structure of the protein–DNA complex. Cell 71(7): 1223–1237.

Harbury PB, Zhang T, Kim PS and Alber T (1993) A switch between two‐, three‐, and four‐stranded coiled coils in GCN4 leucine zipper mutants. Science 262: 1401–1407.

Kammerer RA, Schulthess T, Landwehr R et al. (1998) An autonomous folding unit mediates the assembly of two‐stranded coiled coils. Proceedings of the National Academy of Sciences of the USA 95: 13419–13424.

Krylov D, Mikhailenko I and Vinson C (1994) A thermodynamic scale for leucine zipper stability and dimerization specificity: E and G interhelical interactions. EMBO Journal 13: 1849–1861.

Krylov D, Barchi J and Vinson C (1998) Inter‐helical interactions in the leucine zipper coiled coil dimer: pH and salt dependence of coupling energy between charged amino acids. Journal of Molecular Biology 279: 959–972.

Moitra J, Szilák L, Krylov D and Vinson C (1997) Leucine is the most stabilizing aliphatic amino acid in the d position of a dimeric leucine zipper coiled coil. Biochemistry 36: 12567–12573.

O'Shea EK, Klemm JD, Kim PS and Alber T (1991) X‐ray structure of the GCN4 leucine zipper, a two‐stranded, parallel coiled coil. Science 254: 539–544.

O'Shea EK, Rutkowski R and Kim PS (1992) Mechanism of specificity in the Fos‐Jun oncoprotein heterodimer. Cell 68: 699–708.

Steinmetz MO, Stock A, Schulthess T et al. (1998) A distinct 14 residue site triggers coiled‐coil formation in cortexillin I. EMBO Journal 17: 1883–1891.

Vinson CR, Sigler PB and McKnight SL (1989) Scissors‐grip model for DNA recognition by a family of leucine zipper proteins. Science 246: 911–916.

Zhou N, Kay C and Hodges R (1994) The net energetic contribution of interhelical electrostatic attractions to coiled‐coil stability. Protein Engineering 7(11): 1365–1372.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

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]