Peptide 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.)... 

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 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. 

Fig. 12. Representation of the carboxyl terminal (residues 14-31) moiety of human /3-endorphin (peptide 6, Table 2) on an Edmundson helical wheel [54]. If /3-endorphin chromatographed at any time with a carboxyl terminal amphipathic a-helical structure, the segments incorporating (Leu-14)-(Phe-18)-(Ala-21)-(Asn-15) and (Val-15)-(Ile-22)-(Ala-26) would represent the sites most likely to interact with a reversed phase support.

The largest group of facial amphiphilic peptides consists of the alpha-helical peptides. Facial amphiphilic alpha helices, often referred to as amphipathic alpha helices, are not amphiphilic in their random coil conformation and their amphiphilicity is not directly obvious from then-sequence. However, folding of the peptide into its preferred secondary structure, leads to the formation of an alpha helix, of which the hydrophilic amino acids occupy one face and the hydrophobic amino acids are located at the other face. Alpha-helical peptides have a periodicity of 3.6 amino acid residues per turn, and because of this, for two turns, roughly every third and seventh amino acids are on the same face of the alpha helix. In order to make a helix amphiphilic, the sequence of amino acids should alternate between hydrophobic and hydrophilic every three to four residues, which becomes more clear in a helical wheel representation (Figure 3). An example of such a facial amphiphilic alpha helix is magainin 2, a 23 amino acid antibiotic peptide. Studies have shown that magainin... 

Figure 7 Helical-wheel diagram of the template peptide in the dimeric a-helical coiled-coil configuration emphasizing the heptad repeat motif. The interhelical recognition surface consists of amino acids allowing for hydrophobic packing interactions (positions a and d) and electrostatic interactions (positions e and g). Amino acids at positions b, c, and / lie on the solvent-exposed surface of the helical structure and do not participate in the molecular recognition processes. Arrows indicate the ligation site between a cysteine and an alanine residue.

The structures of synthetic peptides used in the present investigation are shown in Fig. 1. Two amphiphilic a-helical peptide chains containing Lys residues were connected to cyclic octapeptide. The association of two peptide chains should be promoted by the presence of cyclic-peptide template. In addition, two amphiphilic peptide chains are stabilized in water with the hydrophobic surfaces facing each other. The arrangements of hydrophobic and hydrophilic residues are shown as helical wheels in Fig. 2. The... 

To illustrate the power of PISA wheels and dipolar waves to determine the structure of helical peptides and proteins in uniaxiaUy oriented lipid bilayers. Fig. 6a-c show SIMPSON/SIMMOL-simulated PISEMA spectra of an ideal 18-residue a-helix with a tilt angle of 10°-30° relative to Bq. In these simulations, we have tried to mimic experimental conditions by including a random distribution of the principal components of the chemical shift tensor and the dipolar coupling. The chemical shift distribution is 6 ppm for each principal element and has been established as follows we obtained — 85000 N isotropic chemical shifts reported to the BioMagResBank and selected only the — 31000 located in helical secondary stractures to have a data set independent on secondary chemical shifts. The standard deviation on the N chemical shifts for these resonances was — 6 ppm. With the lack of other statistically reliable experimental methods to establish such results for the individual principal elements of the N CSA tensor, we assumed the above variation of 6 ppm for all three principal elements. The variation of the H- N dipolar coupling was estimated by investigating the structures for a small number of a-helical membrane proteins for which the structures were established by liquid-state NMR spectroscopy. These showed standard deviations... 

Another characteristic of the secondary structure of protein includes the occurrence of hydrophobic amino acids clustered on the surface of globular proteins. It seems that hydrophobic amino acids occur regularly as the 20th amino acid in the primary structure of the peptide. These amino acids are rotated on an angle of 100° on the axis of the protein such that the globular proteins have all hydrophobic amino acids clustered to one side on the helical surface of protein, whereas the other end of the globular protein contains polar amino acids. Thus, it is possible to generate a wheel of amino acids in a protein in which the hydrophobic amino acids are clustered on one side of the helix, and the other side contains polar amino acids. 

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