Transmembrane Peptides Stabilize Inverted Cubic Phases in a Biphasic Length-dependent Manner: Implications for Protein-induced Membrane Fusion.
Item Type:Journal Article
Citation:Siegel, D. P., Cherezov, V., Greathouse, D. V., Koeppe II, R. E., Killian, J. A., Caffrey, M., Transmembrane Peptides Stabilize Inverted Cubic Phases in a Biphasic Length-dependent Manner: Implications for Protein-induced Membrane Fusion., Biophysical Journal, 90, 2006, 200-211
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WALP peptides consist of repeating alanine-leucine sequences of different lengths, flanked with tryptophan ``anchors?? at each end. They form membrane-spanning a-helices in lipid membranes, and mimic protein transmembrane domains. WALP peptides of increasing length, from 19 to 31 amino acids, were incorporated into N-monomethylated dioleoylphosphatidylethanolamine (DOPE-Me) at concentrations up to 0.5 mol%peptide.When pure DOPE-Me is heated slowly, the lamellar liquid crystalline (La) phase first forms an inverted cubic (QII) phase, and the inverted hexagonal (HII) phase at higher temperatures. Using time-resolved x-ray diffraction and slow temperature scans (1.5 C/h), WALP peptides were shown to decrease the temperatures of QII and HII phase formation (TQ and TH, respectively) as a function of peptide concentration. The shortest and longest peptides reduced TQ the most, whereas intermediate lengths had weaker effects. These findings are relevant to membrane fusion because the first step in the La/QII phase transition is believed to be the formation of fusion pores between pure lipid membranes. These results imply that physiologically relevant concentrations of these peptides could increase the susceptibility of biomembrane lipids to fusion through an effect on lipid phase behavior, and may explain one role of the membrane-spanning domains in the proteins that mediate membrane fusion.
Science Foundation Ireland (SFI)
Author: CAFFREY, MARTIN
Type of material:Journal Article
Series/Report no:Biophysical Journal
Availability:Full text available
Subject (TCD):Next Generation Medical Devices