Self-association of model transmembrane alpha-helices is modulated by lipid structure.
We have developed a fluorescence quenching method using peptides containing 3,5-dibromotryrosine to measure oligomerization of model transmembrane alpha-helices in lipid bilayers. Peptides of the type Ac-LysLysGlyLeu(m)XLeu(n)LysLysAla-amide where X is tryptophan or 3,5-dibromotyrosine were found to form heterodimers in bilayers of phosphatidylcholine in the liquid-crystalline phase. The free energy of dimer formation changed little with increasing number of Leu residues from 16 to 22 but increased with increasing phospholipid fatty acyl chain length, with a slope of about 0.5 kJ mol(-1) per fatty acyl chain carbon. Peptides were excluded from lipid in the gel phase, resulting in increased levels of oligomerization. Addition of cholesterol to form the liquid-ordered state led to increased dimerization but without phase separation. The presence of phosphatidylethanolamine had little effect on dimerization.
Mall
S
S
Division of Biochemistry and Molecular Biology, School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK.
Broadbridge
R
R
Sharma
R P
RP
East
J M
JM
Lee
A G
AG
D000595:Amino Acid Sequence; D019281:Dimerization; D005453:Fluorescence; D005782:Gels; D066298:In Vitro Techniques; D008051:Lipid Bilayers / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry*; D008567:Membranes, Artificial; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D013816:Thermodynamics; D014443:Tyrosine / Q000031:analogs & derivatives / Q000737:chemistry
D005782:Gels; D008051:Lipid Bilayers; D008565:Membrane Proteins; D008567:Membranes, Artificial; D010455:Peptides; D014443:Tyrosine; C082610:3,5-dibromotyrosine