Self-Association of Model Transmembrane α-Helices Is Modulated by Lipid Structure

• Published in: Biochemistry (Easton) 2001-10, Vol.40 (41), p.12379-12386
• Main Authors: Mall, Sanjay, Broadbridge, Robert, Sharma, Ram. P, East, J. Malcolm, Lee, Anthony G
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Dimerization; Fluorescence; Gels; In Vitro Techniques; Lipid Bilayers - chemistry; Membrane Proteins - chemistry; Membranes, Artificial; Models, Molecular; Peptides - chemistry; Protein Structure, Secondary; Thermodynamics; Tyrosine - analogs & derivatives; Tyrosine - chemistry
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi011075y

We have developed a fluorescence quenching method using peptides containing 3,5-dibromotryrosine to measure oligomerization of model transmembrane α-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.