Position and ionization of Asp in the core of membrane-inserted alpha helices control both the equilibrium between transmembrane and nontransmembrane helix topography and transmembrane helix positioning

Model membrane-inserted Lys-flanked polyLeu peptides (pL peptides) containing one or two Asp substitutions at different positions in their primary sequence are studied with reference to their behavior. At low pH (where the Asp residues were uncharged), the fully transmembrane (TM) state in which the Asp residues were buried in the bilayer core predominated while at higher pH (where the Asp residues were charged), the formation of a truncated TM helix or a shallowly located non-TM state was observed.