Helical wheel structure

In order to examine the possibility of this speculation, an approach using synthetic peptides was made [10]. Three kinds of peptides (H, S, and R) with 16 amino acid residues were synthesized, and their secondary structure and surface properties were investigated to clarify the effects of conformational amphiphilicity. The amino acid compositions of the three peptides were the same (8 Leu and 8 Glu residues), but their sequences were different. The helical wheel structure of peptide H is shown in Fig. 2e [5], As shown in this structure, peptide H was designed to form an amphiphilic a-helix, whereas the other peptides were designed not to show such amphiphilicity, even when... 

FIG. 2 Helical wheel structures of (a) Os,-casein residues 12-23 (b) bovine serum albumin residues 383-396 (c) bovine serum albumin residues 541-555 (d) P-lacto-globubn residues 125-143 and (e) synthetic peptide H. Hydrophobic amino acids are shown by closed circles, hydrophUic charged amino acids by open circles, and hydro-phibc uncharged amino acids by shaded circles. (From Ref. 5.)... 

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 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...

A ferris wheel assembly involving a 1 1 complex of 19 and metallated [18]crown-6 is found in the cationic supermolecule [La(H20)3([ 18]crown-6)] (19+2H) + [48]. The lanthanum ion is coordinated by one calixarene sulfonate group, the [18] crown-6 and three aquo ligands, and the metallated crown sits inside the calixarene cavity. A helical hydrogen bonded chain structure is formed between the cationic assembly, water and chloride ions. The ferris wheel structural motif is also found in Ce3+ complex which simultaneously contains a Russian Doll assembly [44]. 

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... 

G-protein coupled receptors respond to an astonishing variety of activators including short peptides, proteins, biogenic amines, nucleotides, lipids and even photons of light They are single subunit integral membrane proteins with a common seven-transmembrane domain structure in the form of a so-called helical wheel [Fig. 6-21(6)]. 

Figure 1. A. Primary structures of the c-Myc and Max LZs. Sequences are taken from Zervo a al. (26) and renumbered. B. Helical wheel diagram of the c-Myc-Max heterodimeric LZ. Potential interhelical electrostatic interactions have been discussed elsewhere (19,20). In the knobs-into-hole model (9), side-chains (knobs) at position <1 in the heptad repeat pack in the holes formed by consecutive g and a residues and two d positions. Accordingly, Max AsnSn is proposed to pack in the hole formed by Valid, Glu4g, GluSa and LeuSd on the c-Myc LZ. Similarly, Max Asnl9a is proposed to pack in the hole formed by LeulSd, ArglSg, Argl9a and Leu22d.

Schiffer, M., and Edmundson, A, B. Use of helical wheels to represent the structures of proteins and to identify segments with helical potential. Biophys. J. 7, 121-135 (1967). 

Figure 16.8 Model GCN4-p1 peptides, (a) Helical wheel diagram and sequence of GCN4-pl analogue. C = acetamidocysteine. (b) Structures oftrifluoroleucine (L) and trifluorovaline (V) used to stabilize peptide ensembles. The asterisk indicates unresolved stereochemistry, (c) Model structure of GCN4-p1 (PDB code 2ZTA). Side-chains of V and L residues at a and d positions are shown as spheres. Side-chains of Asn residues are shown in stick representation. The structure was generated using MacPyMOL (DeLano Scientific LLC, Palo Alto, CA, U.S.A.).

A very important aspect of solid-state NMR studies of uniaxiaUy oriented peptides is the possibility to directly determine the conformation of the protein in the bilayer. The PISA wheels 2 for regular secondary structures, which may be considered a direct NMR mapping of the so-called helical wheels, help interpreting the experimental spectra. More recently, Opella and co-workers have suggested to exclusively use the effective dipolar couplings in the analysis of such spectra to alleviate uncertainties from small residue/structure-specific variations in the chemical shifts. 

D Correlation Spectroscopy. A simple, quahtative approach has been described for the determination of membrane protein secondary structure and topology in lipid bilayer membranes." The new approach is based on the observation of wheel-like resonance patterns in the NMR H- N/ N polarization inversion with spin exchange at the magic angle (PISEMA) and H/ N HETCOR spectra of membrane proteins in oriented lipid bilayers. These patterns, named Pisa wheels, have been previously shown to reflect helical wheel projections of residues that are characteristic of a-helices associated with membranes. This study extends the analysis of these patterns to P-strands associated with membranes and demonstrates that, as for the case of a-helices, Pisa wheels are extremely sensitive to the tilt, rotation, and twist of P-strands in the membrane and provide a sensitive, visually accessible, qualitative index of membrane protein secondary structure and topology. 

The periodicity of 16 residues per a-helical turn means that if the helix is viewed down its axis, the side chains stick out approximately every 100°, and the helix can be represented by a helical wheel [56], shown in Figure 7. If the a helix is on the outside of the protein, the nature of the sidechains must change from hydrophobic for the part that faces the interior of the protein to hydrophilic for the part of the protein that can interact with solvent. The helix is then described as amphipathic. This is seen in the crystal structure of a... 

Fig. 6 Structural details obtained by lineshape analysis, (a) In KcsA, labeling at any residue position renders a tetramer with potentially four spin labels, (i) Tandem dimer construct (ii) with cys residues in both protomers (control used to evaluate the effects of the intersubunit linker) and (iii) with only one of the protomers containing a cys (used in the analysis), (b) Rigid-limit X-band EPR spectra obtained at pH 7 (thick line, closed state) and at pH 4 (thin line, open state). Right panel, absorption spectra obtained from integration and relative fits obtained with convolution superimposed, (c) Simulated spin- and amplitude-normalized spectra for the two interspin distances in the figure (100% spin labeling efficiency), (d) Helical wheel representation of residues 100-119. Both closed (top) and open (bottom) states are represented as pairs of helical wheel...

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