Leucine zippers, function

The microtubule-associated proteins MAP2 and tau both have two separate functional regions (Lewis et al., 1989). One is the microtubule-binding site, which nucleates microtubule assembly and controls the rate of elongation (by slowing the rate of assembly). The second functional domain shared by MAP2 and tau is a short C-terminal a-helical sequence that can cross-link microtubules into bundles by self-interaction. This domain has some of the properties of a leucine zipper. Likely it is responsible for the organization of microtubules into dense stable parallel arrays in axons and dendrites (Lewis et al., 1989). 

Subunit Mixing in Eukaryotic Regulatory Proteins Several families of eukaryotic transcription factors have been defined based on close structural similarities. Within each family, dimers can sometimes form between two identical proteins (a homodimer) or between two different members of the family (a heterodimer). A hypothetical family of four different leucine-zipper proteins could thus form up to ten different dimeric species. In many cases, the different combinations appear to have distinct regulatory and functional properties. 

An important clue to c-myc function was the discovery in the conserved carboxy-terminal regions of three structural motifs, the leucine zipper (LZ), helix-loop-helix (HLH) and basic region (B). These motifs were originally defined in a number of other sequence-specific DNA-bind-ing proteins but had not previously been found within a single protein. 

Thus, the question in coiled-coil prediction and design is what specific replacements are superimposed on the basic HPPHPPP pattern to direct the functional oligomerization state This question was first tackled by Conway and Parry, who analyzed natural coiled-coil sequences that formed dimers and trimers (Conway and Parry, 1990, 1991). Woolfson and Alber (1995) advanced this approach by comparing amino-acid profiles for these two structures directly. The work that made the biggest impact on this issue, however, was the collaborative experimental study from the Kim and Alber laboratories using the GCN4 leucine-zipper peptide model system and mutants thereof. 

Again, protein-protein contacts allow for specific interaction between different proteins. These contacts are hypothesized to occur by the interaction of hydrophobic domains sometimes called leucine zippers to denote their amino acid composition as well as their function. 

Yo antibody positive PCD sera bind the cdr2 leucine zipper domain and abrogate the ability of cdr2 to interact with c-myc, an interaction that may trigger neuronal apoptosis [193]. This model provides a pathway by which the Yo antibodies may interfere directly with essential intracellular functions, but their relevance in the human disease is still uncertain. 

Richie-Jannetta R, Francis SH, Corbin JD. 2003. Dimerization of cgmp-dependent protein kinase I 3 is mediated by an extensive amino-terminal leucine zipper motif, and dimerization modulates enzyme function. J Biol Chem 278 50070-50079. 

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