Folding amphipathic helices into membranes: amphiphilicity trumps hydrophobicity.
High amphiphilicity is a hallmark of interfacial helices in membrane proteins and membrane-active peptides, such as toxins and antimicrobial peptides. Although there is general agreement that amphiphilicity is important for membrane-interface binding, an unanswered question is its importance relative to simple hydrophobicity-driven partitioning. We have examined this fundamental question using measurements of the interfacial partitioning of a family of 17-residue amidated-acetylated peptides into both neutral and anionic lipid vesicles. Composed only of Ala, Leu, and Gln residues, the amino acid sequences of the peptides were varied to change peptide amphiphilicity without changing total hydrophobicity. We found that peptide helicity in water and interface increased linearly with hydrophobic moment, as did the favorable peptide partitioning free energy. This observation provides simple tools for designing amphipathic helical peptides. Finally, our results show that helical amphiphilicity is far more important for interfacial binding than simple hydrophobicity.
Fernández-Vidal
Mónica
M
Department of Physiology and Biophysics, University of California at Irvine, Irvine, CA 92697-4560, USA.
Jayasinghe
Sajith
S
Ladokhin
Alexey S
AS
White
Stephen H
SH
D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008563:Membrane Lipids / Q000737:chemistry; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000235:genetics; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013501:Surface-Active Agents; D013816:Thermodynamics
D008563:Membrane Lipids; D010455:Peptides; D013501:Surface-Active Agents