Leucine Zipper bzip DNA Complex
The structural details presented in this tutorial are based on the review
by Pabo and Sauer (1992), Annu. Rev. Biochem. 61:1053-1095,
and the tutorial was originally prepared as Rasmol scripts by
Chunlei Su for BMMB 597C.
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Overview
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The bZIP class includes several transcription factors such as
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These proteins regulate the expression of many different genes in
organisms as diverse as fungi, plants, and mammals.
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The leucine zipper is a stretch of amino acids rich in leucine residues
which provide a dimerization motif.
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A leucine zipper forms an amphipathic helix in which the leucine of the zipper
on one protein could protrude from the alpha-helix and interdigitate with
the leucines of the zipper of another protein in parallel to form a coiled
coil.
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The two helices wind around each other, with 3.5 residues per turn, so the
pattern repeats integrally every 7 residues.
The GCN4 / Ap1 Example
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The yeast trasncriptional activator GCN4 is one of the identified
eukaryotic proteins containing the basic region leucine zipper (bZIP) DNA-binding
motif.
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GCN4 protein contains 281 amino acid residues.
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The bZIP motif is located in the carboxy-terminal 56 amino acids.
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The leucine zipper motif contains two distinct subdomains:
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the leucine zipper region mediates dimerization,
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while a basic region contacts the DNA.
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The DNA-binding region functions independently of the rest of the protein.
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At normal cellular concentrations, dimerization is induced by DNA binding.
Overall Structure
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The bZIP dimer is a pair of continuous alpha helices that form a
parallel coiled coil over their carboxy-terminal 30 residues and gradually
diverge toward their aminoo termini to pass through the major groove of the
DNA-binding site.
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Leucine zipper sequence contains a 4-3 heptad repeat of hydrophobic
and nonpolar residues that pack together in a parallel alpha-helical coiled
coil.
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The leucine residue repeats in every seventh position in this sequence and
the conserved leucines play a key role for the dimer formation.
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The GCN4 leucine zipper consists of only four heptad repeats, and it is one
of the shortest leucine zippers in the bZIP family.
DNA / Protein Contacts
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The basic region alpha-helix is anchored in the major groove of the
DNA by an array of positively charged and polar residues, which donate hydrogen
bonds to unesterified oxygens of the phosphodiester backbone.