Using Model Membrane-inserted Hydrophobic Helices to Study the Equilibrium between Transmembrane and Nontransmembrane States

The recent Journal of General Physiology perpsectives on membrane protein insertion (129:351–377) covered many valuable strategies to examine how amino acid sequence determines protein insertion into membranes and the probability that sequences form transmembrane (TM) helices. Each approach described has unique advantages, and a complete exploration of this problem clearly requires combining approaches, including approaches not discussed in the perspectives, such as the use of synthetic hydrophobic helices inserted into model membrane vesicles. Using a diverse set of biophysical methods, several groups have used the latter approach to understand fundamental issues of membrane protein structure and function, including the confi guration of membrane-inserted hydrophobic helices (TM or non-TM), the effect of hydrophobic helices on bilayer structure (and vice versa), and helix–helix interaction (Bechinger, 1996; Hunt et al., 1997; Ren et al., 1997, 1999; Killian, 1998; Webb et al., 1998; Lew et al., 2000, 2003; Mall et al., 2000; Caputo and London, 2003a; Goforth et al., 2003; Liu et al., 2004; Duong-Ly et al., 2005; van Duyl et al., 2005; Aisenbrey et al., 2006; Killian and Nyholm, 2006).