Amphipathic a helices

Residues 50-64 of the GAL4 fragment fold into an amphipathic a helix and the dimer interface is formed by the packing of these helices into a coiled coil, like those found in fibrous proteins (Chapters 3 and 14) and also in the leucine zipper families of transcription factors to be described later. The fragment of GAL4 comprising only residues 1-65 does not dimerize in the absence of DNA, but the intact GAL4 molecule does, because in the complete molecule residues between 65 and iOO also contribute to dimer interactions. 

This discussion puts us in a position to define a set of structural and evolutionary objects the tracing of whose history via homology, as implied by sequence similarity, is the primary aim of sequence analyses. The simple view of protein folding produces a small set of structural components to consider. This is the set of regular secondary structures the amphipathic a helix, the transmembrane or hydrophobic a. helix, the... 

Apolipoprotein A-I is the primary protein component of HDL.23 2513 Most of the 243 residues consist of a nearly continuous amphipathic a helix with kinks at regularly spaced proline residues.26 28 Two disulfide-linked ApoA-I molecules may form a belt that encircles the discoid lipoprotein.2513 ApoA-II is the second major HDL protein, but no dearly specialized function has been identified.29 30 ApoA-I, II, and IV, apoC-I, II, and III, and apoE all have multiple repeats of 22 amino acids with sequences that suggest amphipathic helices. Tire 391-residue ApoA-IV has 13 tandem 22-residue repeats. Proline and glycine are present in intervening hinge regions.23 This may enable these proteins to spread over and penetrate the surfaces of the lipoprotein micelles. Most of these proteins are encoded by a related multigene family.7 303... 

Thus, the Phe analogue coiled coil Fc is less stable than the Leu analogue coiled coil Lc (Figure 3) this reflects the preferred hydrophobic interactions of Leu compared to Phe. Thus, the difference between the retention time of the single-stranded amphipathic a-helix and its respective two-stranded oxidized coiled coil is less for peptide F than for peptide L, since the coiled-coil structure of the former (F ) is unfolded to a greater extent than that of the latter (L ) by the hydrophobic stationary phase and, hence, exposes more of its hydro-phobic surface area to the RP matrix. 

THE AMPHIPATHIC a HELIX A MULTIFUNCTIONAL STRUCTURAL MOTIF IN PLASMA APOLIPOPROTEINS... 

The amphipathic a helix, defined as an a helix with opposing polar and nonpolar faces oriented along its long axis, is a common secondary structural motif in biologically active peptides and proteins. The discovery of this structural motif was made by studying space-filling models of... 

The 1 l-mer/22-mer evolutionary pathway for apolipoproteins can be explained as a result of the 3.6 amino acid residues per turn periodicity of an 0 helix 11 residues form three complete turns of an a helix. Consequently, tandem duplication of an 11-residue amphipathic a helix produces a 22-residue amphipathic a helix (Fig. 5). There is little twist (20° or less) between the polar and nonpolar faces of the two identical 11-mer halves (Segrest et al., 1990 Anantharamaiah et al., 1990a). This 11-mer/ 22-mer motif also means that continuous amphipathic helices significantly longer than 22 residues can exist e.g., there will be a twist of 40° or less between the polar and nonpolar faces of two tandem identical 22-mer amphipathic helices (Fig. 5). 

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