EFFECT OF SEQUENCE HYDROPHOBICITY AND BILAYER WIDTH UPON THE MINIMUM LENGTH REQUIRED FOR THE FORMATION OF TRANSMEMBRANE HELICES IN MEMBRANES

The minimum hydrophobic length necessary to form a transmembrane (TM) helix in membranes was investigated using model membrane-inserted hydrophobic helices. The fluorescence of a Trp at the center of the sequence and its sensitivity to quenching were used to ascertain helix position within the membrane. Peptides with hydrophobic cores composed of polyLeu were compared to sequences containing a poly 1:1 Leu:Ala core (which have a hydrophobicity typical of natural TM helices). Studies varying bilayer width revealed that the polyLeu core peptides predominately formed a TM state when the bilayer width exceeded hydrophobic sequence length by (i.e. when negative mismatch was) up to ∼11–12Å (e.g. the case of a 11–12 residue hydrophobic sequence in bilayers with a biologically relevant width, i.e. dioleoylphosphatidylcholine [DOPC] bilayers), while polyLeuAla core peptides formed predominantly TM state with negative mismatch of up to 9Å (a 13 residue hydrophobic sequence in DOPC bilayers). This indicates that minimum length necessary to form a predominating amount of a TM state (minimum TM length) is only modestly hydrophobicity-dependent for the sequences studied here, and a formula that defines the minimum TM length as a function of hydrophobicity for moderately-to-highly hydrophobic sequences was derived. The minimum length to form a stable TM helix for alternating LeuAla sequences, and that for sequence