Helical wheels

A convenient way to illustrate the amino acid sequences in helices is the helical wheel or spiral. Since one turn in an a helix is 3.6 residues long, each residue can be plotted every 360/3.6 = 100° around a circle or a spiral, as shown in Figure 2.4. Such a plot shows the projection of the position of the... 

Figure 2.4 The helical wheel or spiral. Amino acid residues are plotted every 100° around the spiral, following the sequences given in Table 2.1. The following color code is used green Is an amino acid with a hydrophobic side chain, blue is a polar side chain, and red is a charged side chain. The first helix is all hydrophobic, the second is polar on one side and hydrophobic on the other side, and the third helix is all polar.

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,...

In globular protein structures, it is common for one face of an a-helix to be exposed to the water solvent, with the other face toward the hydrophobic interior of the protein. The outward face of such an amphiphilic helix consists mainly of polar and charged residues, whereas the inward face contains mostly nonpolar, hydrophobic residues. A good example of such a surface helix is that of residues 153 to 166 of flavodoxin from Anabaena (Figure 6.24). Note that the helical wheel presentation of this helix readily shows that one face contains four hydrophobic residues and that the other is almost entirely polar and charged. 

FIGURE 10.24 A helical wheel model of halorhodopsin. The amino acids facing the polar, hydrophilic core of the protein are shown. Of these 60 residues, 36 are conserved between halorhodopsin and bacteriorhodopsin. (Adapted from OesterMt, D., and Tittor, f, 1989. Treads ia Biochemical Scieaces 14 57—61.)... 

Fig. 2.39 Schematic representation of the projection of idealized ji- and y-peptide helices in a plane perpendicular to the helix axis and comparison with the helical wheel of the natural a-helix...

Fig. 2.40 Sequences and helical wheel representation of amphiphilic 2.5,2-helical jS-pep-tide 17-mers evaluated for antimicrobial activity [234, 248]. These peptides are exclusively composed of hydrophobic trans-ACPC...

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)...

Figure 3.3 Molecular structure of G-protein-coupled receptors. In (a) the electron density map of bovine rhodopsin is shown as obtained by cryoelectron microscopy of two-dimensional arrays of receptors embedded in lipid membrane. The electron densities show seven peaks reflecting the seven a-helices which are predicted to cross the cell membrane. In (b) is shown a helical-wheel diagram of the receptor orientated according to the electron density map shown in (a). The diagram is seen as the receptor would be viewed from outside the cell membrane. The agonist binding pocket is illustrated by the hatched region between TM3, TM5 and TM6. (From Schertler et al. 1993 and Baldwin 1993, reproduced from Schwartz 1996). Reprinted with permission from Textbook of Receptor Pharmacology. Eds Foreman, JC and Johansen, T. Copyright CRC Press, Boca Raton, Florida...

Figure 1 A helical wheel diagram of a dimeric coiled-coil. Letters a through g denote the seven amino acid residues of a heptad repeating unit. 

Figure 14.3 Helical wheel diagram of the YZl peptide and the schematic representation of the staggered dimer formation with an axial displacement of three heptad repeating units, which promote elongation into coiled coil fibrils. Reprinted from Zimenkov et al. (2004). Copyright 2004 Elsevier Science.

Fig. 7. Helical wheel and sequence representation of the parental homodimeric coiled coil. The substitution positions within the hydrophobic domain are highlighted with open squares and those in the charged domain with open circles. Their interaction partners are highlighted with shaded squares and circles, respectively. The arrows mark the ligation site of nucleophilic and electrophilic fragments. (See Colour Plate Section at the end of this book.)...

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... 

Several mammalian leucine zipper proteins bind to the CCAAT sequence (Table 28-1) and are, therefore, as a family designated C/EBP.361 366 367 A 30-residue segment of C/EBP contains four leucine residues at 7-residue intervals. When plotted as a helical wheel (Fig. 2-20) the four leucines are aligned on one side.368 Similar sequences are present in the proteins cMyc, cjun, and cFos and in GCN4. These observations suggested that if the peptide sequence forms an a helix, the leucine side chain from two identical subunits or closely related proteins might interdigitate in... 

The coiled-coil library sequence and helical-wheel diagram of this coiled-coil template is shown in Scheme 9. 

Helical-Wheel Diagram of Template-Ligand Interactions... 

Use of the Helical Wheel Diagram A helical wheel is a two-dimensional representation of a helix, a view along its central axis (see Fig. 11 29b see also Fig. 4-4d). Use the helical wheel diagram below to determine the distribution of amino acid residues in a helical segment with the sequence -Val-Asp Arg Val Phe Ser Asn Val-Cys Thr Ilis Leu Lys "I1 hr Leu Gln-Asp-Lys-... 

Answer A helical wheel is a two-dimensional representation of a helix obtained by projecting the helix down its central axis. An a helix contains 3.6 residues per turn, so each amino acid in the helix lies 100° around the axis from the previous residue (360°/turn)/(3.6 residues/tum) = 100° per residue. For the 18 amino acid helix considered here, the 18 vertices are separated by 20° increments. If there were a 19th residue, it would lie under the first residue on the projection, but five turns down the helix 5 turns X 0.54 nm/tum (pitch for an a helix) = 2.70 nm behind residue 1. To complete the diagram, follow the lines from residue 1 to residue 2, and so on, numbering the residues. Then, using the sequence given, label each residue with its one-letter abbreviation and a characterization of its R group properties—P for polar, and N for nonpolar. 

---