Different membrane anchoring positions of tryptophan and lysine in synthetic transmembrane alpha-helical peptides

Specific interactions of membrane proteins with the membrane interfacial re gion potentially define protein position with respect to the lipid environm ent. We investigated the proposed roles of tryptophan and lysine side chain s as "anchoring" residues of transmembrane proteins. Model systems were emp loyed, consisting of phosphatidylcholine lipids and hydrophobic alpha-helic al peptides, flanked either by tryptophans or lysines, Peptides were incorp orated in bilayers of different thickness, and effects on lipid structure w ere analyzed. Induction of nonbilayer phases and also increases in bilayer thickness were observed that could be explained by a tendency of Trp as wel l as Lys residues to maintain interactions with the interfacial region, How ever, effects of the two peptides were remarkably different, indicating aff inities of Trp and Lys for different sites at the interface, Our data suppo rt a model in which the Trp side chain has a specific affinity for a well d efined site near the lipid carbonyl region, while the lysine side chain pre fers to be located closer to the aqueous phase, near the lipid phosphate gr oup. The information obtained in this study may further our understanding o f the architecture of transmembrane proteins and may prove useful for refin ing prediction methods for transmembrane segments.