Helices alpha, amphipathic

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. 

Segrest MP et al The amphipathic alpha-helix A multifunctional structural motif in plasma lipoproteins. Adv Protein Chem... 

A synthetic peptide has been designed to mimic the effects of viral fusogenic properties (114,115). It consists of 30 amino acids with the major repeat of Glu-Ala-Leu-Ala so, it is referred to as a GALA peptide. It undergoes a conversion from an aperiodic conformation at neutral pH and becomes an amphipathic alpha helix at pH 5. In the more acidic environment, the peptide interacts with lipid bilayers (114,115). GALA has been incorporated into transferrin-targeted liposome, with the effect of significantly... 

Kojima, S., Kuriki, Y., Yoshida, T., Yazaki, K., and Miura, K. (1997). Fibril formation by an amphipathic alpha-helix-forming polypeptide produced by gene engineering. Proc. Japan Acad. B Phys. Biol. Sci. 73, 7—11. 

Giniger E, Ptashne M. Transcription in yeast activated by a putative amphipathic alpha helix linked to a DNA binding unit. Nature. 1987 330 670-672. 

Torres AM, Bansal PS, Sunde M, Clarke CE, Bursill JA, Smith DJ, et al. Structure of the HERG K+ channel S5P extracellular linker role of an amphipathic alpha-helix in C-type inactivation. J Biol Chem 2003 278 42136-48. 

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. 

Zaiou M, Arnold KS, Newhouse YM, Innerarity TL, Weisgraber KH, Segall ML, Phillips MC, Lund-Katz S. Apolipoprotein E -low density lipoprotein receptor interaction. Influences of basic residue and amphipathic alpha-helix organization in the ligand. J Lipid Res 2000 41 1087-1095. 

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... 

Amphipathic helix. Designation of a protein alpha helix in which polar and apolar amino acid side chains align over opposing planes. These secondary structure elements play an important role in proteins that do not interact with membranes via transmembrane segments. 

RCSB PDB (www.rcsb.org) of PDB ID 2GLH (G. Andreotti, B. L. Mendez, P. Amodeo, M. A. Morelli, H. Nakamuta, A. Motta, (2006) Structural determinants of salmon calcitonin bioactivity tbe role of the Leu-based amphipathic alpha-helix,/. Biol. Chem., 281, 24193-24203). 

G. Andreotti, et al. Structural determinants of salmon calcitonin bioactivity The role of the Leu-based amphipathic alpha-helix. (0021-9258 (Print)). 

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