Alpha helices, amphipathic hydrophobic

While lipoproteins are the products of many different genes, the major apolipoproteins share properties distinguishing them from most lipid-free and membrane-associated proteins. For example, apolipoproteins consist of a single polypeptide chain that has relatively little tertiary structure. Most apolipoproteins contain stretches of amphipathic alpha-helix, whose hydrophobic face can be turned to the lipid surface of the particle. The apolipoproteins are flexible, as is reflected in their unusually small free energy of unfolding. As these apolipoproteins expand and contract at the cell surface, different protein domains are exposed that are detectable with monoclonal antibodies. These properties reflect the role of apolipoproteins at the surface of lipoprotein particles whose size changes as they circulate. 

FIGURE 6.24 (a) The alpha helix consisting of residues 153-166 (red) in flavodoxin from Anahaena is a surface helix and is amphipathic. (b) The two helices (yellow and blue) in the interior of the citrate synthase dimer (residues 260-270 in each monomer) are mostly hydrophobic, (c) The exposed helix (residues 74-87—red) of calmodulin is entirely accessible to solvent and consists mainly of polar and charged residues. 

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... 

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