GUIDELINES FOR MEMBRANE-PROTEIN ENGINEERING DERIVED FROM DE-NOVO DESIGNED MODEL PEPTIDES

Notwithstanding great advances in the engineering and structural analy sis of globular proteins, relatively limited success has been achieved with membrane proteins-due largely to their intrinsic high insolubili ty and the concomitant difficulty in obtaining crystals. Pi-ogress wit h de novo synthesis of model membrane-interactive peptides presents an opportunity to construct simpler peptides with definable structures, and permits one to approach an understanding of the properties of the membrane proteins themselves. In the present article, we review how ou r laboratory and others have used peptide approaches to assess the det ailed intel actions of peptides with membranes, and primary folding at membrane surfaces and in membranes. Structural studies of model pepti des identified the existence of a ''threshold hydrophobicity,'' which controls spontaneous peptide insertion into membranes. Related studies of the relative helicity of peptides in organic media such as n-butan ol indicate that the helical propensity of individual residues-not sim ply their hydrophobicity-may dictate the conformations of peptides in membranes. The over-all experimental results provide fundamental guide lines for membrane protein engineering. (C) 1998 John Wiley & Sons, In c.