Leucine zipper domain

Activator Protein-1 (API) comprises transcriptional complexes formed by dimers of members oftheFos, Jun, and ATF family of transcription factors. These proteins contain basic leucine zipper domains that mediate DNA binding and dimerization. They regulate many aspects of cell physiology in response to environmental changes. 

Figure 39-15. The leucine zipper motif. A shows a helical wheel analysis of a carboxyl terminal portion of the DNA binding protein C/EBP. The amino acid sequence is displayed end-to-end down the axis of a schematic a-helix. The helical wheel consists of seven spokes that correspond to the seven amino acids that comprise every two turns of the a-helix. Note that leucine residues (L) occur at every seventh position. Other proteins with "leucine zippers" have a similar helical wheel pattern. B is a schematic model of the DNA binding domain of C/EBP. Two identical C/EBP polypeptide chains are held in dimer formation by the leucine zipper domain of each polypeptide (denoted by the rectangles and attached ovals). This association is apparently required to hold the DNA binding domains of each polypeptide (the shaded rectangles) in the proper conformation for DNA binding. (Courtesy ofS McKnight)...

Structural analysis indicates that the fos and jun proteins belong to a class of DNA-binding proteins that share the conserved structural motif known as the leucine zipper (see fig. 31.21). Thus, the dimerization of these two proteins is mediated by hydrophobic interaction between the leucine side chains of two leucine zipper domains. 

Leucine zipper proteins have been shown to interact with their cognate recognition sites as dimers (Landschulz et al., 1988). This dimer formation is mediated by the leucine zipper domain and is absolutely required for DNA binding (Hu et al., 1990 and references therein). We employed the method of Hope Struhl (1987) to investigate the ability of GBF-1 to form dimers in the presence of DNA. Different portions of the cDNA... 

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. 

Ransone LJ, Visvader J, Sassone-Corsi P, Verma IM. 1989. Fos-Jun interaction Mutational analysis of the leucine zipper domain of both proteins. Genes Dev 3 770-781. 

Surks HK, Mendelsohn ME. 2003. Dimerization of cgmp-dependent protein kinase la and the myosin-binding subunit of myosin phosphatase Role of leucine zipper domains. Cell Signal 15 937-944. 

Figure 13.12. The Nrf family and Maf family transcription factors. The basic domain is involved in DNA binding and the leucine zipper domain is a dimerization module with other basic-leucine zipper transcription factors. Small Maf proteins such as MafK and MafG het-erodimerize with Nrf2 for binding and activation of the ARE.

The DNA-binding domain of the yeast GCN4 transcription factor mentioned earlier is a leucine-zipper domain. X-ray crystallographic analysis of complexes between DNA and the GCN4 DNA-binding domain has shown that the dimeric protein contains two extended a helices that grip the DNA molecule, much like a pair of scissors, at two ad-... 

Doi, J., H. Takemori, X.Z. Lin, N. Horike, Y. Katoh, and M. Okamoto (2002). Salt-inducible kinase represses cAMP-dependent protein kinase-mediated activation of human cholesterol side chain cleavage cytochrome P450 promoter through the CREB basic leucine zipper domain. J. Biol. Chem. Ill, 15629-15637. 

The relative rates of diffusion and reaction are important in the regulation of biochemical pathways. Transcription factors are proteins that bind to specialized regions of DNA and thereby facilitate transcription by RNA polymerase. The binding of one class of transcription factors, the basic leucine zipper (bZIP) proteins, is illustrated in Figure 4.30. The bZIP factors have a C-term-inal leucine zipper domain, a basic region that binds to DNA, and a domain that is important for transcriptional regulation. The bZIP factors must dimerize for transcriptional activity and, therefore, it is usually assumed that dimerization occurs before DNA binding (dimer pathway). A recent study shows... 

CCAAT/enhancer-binding proteins (C/EBPs) are a family of transcription factors that contain a basic leucine zipper domain at the C-terminus that is involved in... 

FIP-2, also called NEMO-related protein, contains two leucine zipper domains. Overexpression of FIP-2 does not cause cell death, but can reverse the protective effect of 14.7K on cell death induced by overexpression of the TNFR intracellular domain or RIP (Li et al. 1998). FIP-1 is identical to RagA and belongs to the family of small GTPases (Li et al. 1997). It does not cause cell death but forms ternary complexes with 14.7K and TCTEL, a component of the microtubule motor protein dynein (Horwitz 2001). It will be interesting to see whether these interactions of 14.7K are also detectable during virus infection and whether they influence the TNF signal cascade. 

Li Y, Kang J, Horwitz MS (1998) Interaction of an adenovirus E3 14.7-kilodalton protein with a novel tumor necrosis factor ot-inducible cellular protein containing leucine zipper domains. Mol Cell Biol 18 1601-1610... 

Martinez-FP Tang O. Leucine zipper domain is required for Kaposi sarcoma-associated heipesvinis (KSHV) K-bZIP protein to interact with histone deacetylase and is important for KSHV replication. J Biol Chem. 2012 287 15622-34. 

Banta and co-workers have introduced a series of functional protein domains into ACiqA hydrogels.In a proof-of-concept, fluorescent protein domains (either red fluorescent protein (RFP) or green fluorescent protein (GFP)) were fused to ACiqA proteins between the disordered Cio domain and one of the leucine zipper domains to make an asymmetrical tetrablock protein polymer. These fusion proteins readily assembled into hydrogels and are more stable than (i.e., do not erode as quickly as) the related ACjqA hydrogels. The increased stability may be due to the asymmetry of the fusion proteins, which... 

---