MECHANISMS FOR THE MODULATION OF MEMBRANE BILAYER PROPERTIES BY AMPHIPATHIC HELICAL PEPTIDES

The amphipathic helix, in which hydrophobic and hydrophilic residues a re grouped on opposing faces, is a structural motif found in many pept ides and proteins that bind to membranes. One of the physical properti es of membranes that can be altered by the binding of amphipathic heli ces is membrane monolayer curvature strain. Class A amphipathic helice s, which are present in exchangeable plasma lipoproteins, can stabiliz e membranes by reducing negative monolayer curvature strain, proline-p unctuated class A amphipathic helical segments are particularly effect ive in this regard. This property is suggested to be associated with s ome of the beneficial biological effects of this protein. On the other hand, lytic amphipathic helical peptides can act by increasing negati ve curvature strain or by forming pores composed of helical clusters. Thus, different amphipathic helical peptides can be membrane stabilizi ng or be lytic to membranes, depending on the structural motif of the helix, which in rum determines the nature of its association with memb ranes. Features of these peptides that are responsible for their speci fic properties are discussed. (C) 1995 John Wiley & Sons, Inc.