Transmembrane Model Peptides – A Powerful Tool to Investigate Protein - Lipid Interactions

Abstract

The function of membrane proteins depends in many cases on the properties of the surrounding lipid environment, including the membrane thickness, fluidity and composition. Still, it is not completely understood how membrane proteins are influenced by the membrane, which is for a large part due to the difficulties to study these hydrophobic systems. This has initiated the use of synthetic transmembrane model peptides mimicking transmembrane segments of membrane proteins, which offers several advantages. The structure of these model peptides can be varied systematically and any labels needed for investigation using biophysical techniques can be easily incorporated during peptide synthesis. Such designed transmembrane peptides are increasingly being used for the systematic investigations on how membrane properties and peptide composition influence the orientation and dynamics of transmembrane segments. Frequently used model peptides are the WALP and KALP peptides, consisting of a hydrophobic stretch of alternating leucines and alanines flanked at both ends by a pair of tryptophans and lysines, respectively. Chapter 1 contains a general introduction to biomembranes, the use and design of transmembrane model peptides and an overview of results obtained using model peptides. In chapter 2, a study aiming at elucidation of the nature of the previously suggested preferential interaction between tryptophans and cholesterol is presented. 2H NMR (Nuclear Magnetic Resonance) and FRET (F