GCN4 transcription factor

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-... 

Figure 2 illustrates how changes in ellipticity as a function of temperature and concentration have been used to determine the enthalpy of folding of a peptide derived from the coiled-coil domain of the yeast GCN4 transcription factor, which undergoes... 

The leucine zipper motif (see Chapter 3) was first recognized in the amino acid sequences of a yeast transcription factor GCN4, the mammalian transcription factor C/EBP, and three oncogene products, Fos, Jun and Myc, which also act as transcription factors. When the sequences of these proteins are plotted on a helical wheel, a remarkable pattern of leucine residues... 

Figure 10.17 Amino acid sequences, represented as a helical wheels with 3.5 residues per turn, of a region of 28 residues from the DNA-binding domains of the transcription factors (a) GCN4, (b) Max,...

Figure 10.28 Schematic diagram of the binding of the transcription factor Max to DNA. The two monomers of Max (blue and green) form a dimer through both the helix-loop-helLx regions which form a four-helix bundle like MyoD, and the zipper regions, which are arranged in a coiled coil. The N-terminal basic regions bind to DNA in a way similar to GCN4 and MyoD. (Adapted from A.R. Ferre-D Amare et al., Nature 363 38-4S, 1993.)...

In addition to Sid, Cdc4 targets a number of other important substrates including the replication factor Cdc6, the transcription factor Gcn4 and the... 

Fig. 1.7. Basic leudne zipper and heltx-loop-heltx motif in complex with DNA. A) The basic leucine zipper of the transcription activator GCN4 of yeast consists of two slightly curved a-hehces, which dimerize with the help of the leucine zipper motif. The sequence specific binding of DNA occurs via the basic ends of the two helices. They insert themselves into the major groove of the DNA. B) The helix-loop-helix motif of the eucaryotic transcription factor Max complexed with DNA. Molscript drawing (Kraulis 1991).

The translation of certain mRNAs, including that encoding the transcription factor GCN4 of yeast, is stimulated rather than inhibited according to the above mechanism. In this case there exists a complex interaction between several initiation sites. 

B) Helical wheel representation of residues 2-31 of the coiled coil portion of the leucine zipper (residues 249-281) of the related transcription factor GCN4 from yeast. The view is from the N terminus and the residues in the first two turns are circled. Heptad positions are labeled a-g. Leucine side chains at positions d interact with residues d and e of the second subunit which is parallel to the first. However, several residues were altered to give a coiled coil that mimics the structure of the well-known heterodimeric oncoproteins Fos and Jun (see Chapter 11). This dimer is stabilized by ion pairs which are connected by dashed lines. See John et al.172... 

Figure 5-36 Stereoscopic diagrams showing some of the interactions between an N-terminal helical domain of the yeast transcription factor GCN4-bZIP, a leucine zipper protein, and a specific palindromic DNA binding site ...

Enhancer elements and transcription factors 5 -ATGA(C/G)TCAT AP-1, cjun, GCN4 (yeast)... 

Fig. 3. The structure of the 33-residue region of yeast transcription factor GCN4 is a two-stranded coiled coil, and is viewed here perpendicular to its long axis. The chains each have a heptad substructure and an a-helical conformation. Because GCN4 contains leucine residues in each d position, except for the most C-terminal one, the structure is commonly referred to as a leucine zipper (PDB coordinate reference number 2ZTA). The pitch length of the left-handed coiled coil has an average value of about 20.4 nm (Harbury et al, 1993 Kuhnel et al, 2004).

Coiled-coil motifs have been known to play roles in conformational switching in natural proteins for some time (Oas and Endow, 1994). The key examples are influenza hemagglutinin (Bullough et al., 1994 Carr and Kim, 1993 Carr et al., 1997), and the heat shock transcription factor (Rabindran et al., 1993). Furthermore, an engineered form of GCN4-pl, with Asn-16 replaced by Ala, switches from dimer to trimer upon addition of... 

The a-helix is the most abundant secondary structural element, determining the functional properties of proteins as diverse as a-keratin, hemoglobin and the transcription factor GCN4. The average length of an a-helix in proteins is approximately 17 A, corresponding to 11 amino acid residues or three a-helical turns. In short peptides, the conformational transition from random coil to a-helix is usually entropically disfavored. Nevertheless, several methods are known to induce and stabilize a-helical conformations in short peptides, including ... 

The various aspects of our approach are demonstrated below within the context of a two-stranded coiled-coil polypeptide model that was designed to mimic the disulfide cross-linked two-stranded coiled-coil from the yeast transcription factor GCN4 [68-74] which was used by Hochstrasser and coworkers in their pioneering SM-FRET experiment. [30,33]... 

It is also of interest to compare our results with experiment. The experimental study most closely related to the model considered here is the SM-FRET assay by Hochstrasser and co-workers on the disulfide cross-linked two-stranded coiled-coil from the yeast transcription factor GCN4. [30,33] Our results appear to be consistent with many of the experimental observations reported in Refs. [30,33], For example, surface-immobilization in the folded state has a rather small effect on the R distribution, the folded and unfolded states are seen to correspond to narrow and broad R distributions, respectively, and conformational dynamics is seen to be characterized by a wide dynamical range in the midpoint and unfolded states. Our analysis can also help in the interpretation of the experimental results. For example, surface-... 

Cranz S, Berger C, Baici A, Jelesarov 1, Bosshard HR. Monomeric and dimeric bZlP transcription factor GCN4 bind... 

Fig. 1. Result of oligo-analysis on the upstream sequences of the 27 genes responding to nitrogen depletion. The first discovered pattern corresponds to the binding site of the GATA transcription factors and the second one to GCN4.

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