Structures of Gramicidins A, B, and C Incorporated into Sodium Dodecyl Sulfate Micelles^,

Abstract

Gramicidins A, B, and C are the three most abundant, naturally occurring analogues of this family of channel-forming antibiotic. GB and GC differ from the parent pentadecapeptide, GA, by single residue mutations, W11F and W11Y, respectively. Although these mutations occur in the cation binding region of the channel, they do not affect monovalent cation specificity, but are known to alter cation-binding affinities, thermodynamic parameters of cation binding, conductance and the activation energy for ion transport. The structures of all three analogues incorporated into deuterated sodium dodecyl sulfate micelles have been obtained using solution state 2D-NMR spectroscopy and molecular modeling. For the first time, a rigorous comparison of the 3D structures of these analogues reveals that the amino acid substitutions do not have a significant effect on backbone conformation, thus eliminating channel differences as the cause of variations in transport properties. Variable positions of methyl groups in valine and leucine residues have been linked to molecular motions and are not likely to affect ion flow through the channel. Thus, it is concluded that changes in the magnitude and orientation of the dipole moment at residue 11 are responsible for altering monovalent cation transport.

The Preference of Tryptophan for Membrane Interfaces

“…Each gA subunit has four Trps, which in the singlestranded (SS) ␤-helical channel structure are localized near the membrane/water interface ( Fig. 1C) (22,23). Changing the membrane environment (24,25) or the amino acid sequence (18,19,26) can alter the gA folding preference, in some cases promoting the folding into double-stranded (DS) dimeric structures (Fig.…”

Systematic Peptide Engineering and Structural Characterization to Search for the Shortest Antimicrobial Peptide Analogue of Gaegurin 5

“…3B). Tryptophan, with an indole side chain bearing both hydrophobic and hydrophilic properties, is the most representative amino acid with an inherent membrane interaction ability, and it often plays an important role by anchoring proteins within the lipid bilayer (41)(42)(43)(44)(45).…”

“…Tryptophanyl Substitution of GGN5 N11 -Tryptophan has been rarely found in natural antimicrobial peptides with amphipathic helical structures, although some antimicrobial peptides in different structural groups are particularly rich in tryptophan (42)(43)(44)(45). Recently, we found that a single tryptophanyl substitution at position 16 in the ⌬ 24 -37 GGN4 (or GGN4 N23 ), a synthetic, inactive fragment of gaegurin 4 (GGN4), generated strong antimicrobial activity without significant hemolytic activity (21,34).…”

Foldameric β‐H18/20P Mixed Helix Stabilized by Head‐to‐Tail Contacts: A Way to Higher‐Order Structures

“…This phenomenon can be observed in gramicidin A, for example, in which axial self-recognition takes place in the membrane environment. [32] In peptidic foldamers, axial helix-helix interactions were recently observed in the self-association of the β-peptidic H12 helix to form the large-diameter β-H18 helix. [33] In this work we report on the serendipitous discovery of the largest-diameter β-peptidic mixed helix known to date, the β-H18/20 helix, the formation of which is solventdependent and its folding occurs cooperatively through head-to-tail interactions in solution.…”