HYDROPHOBIC MISMATCH AND THE INCORPORATION OF PEPTIDES INTO LIPID BILAYERS - A POSSIBLE MECHANISM FOR RETENTION IN THE GOLGI

Preferential interaction of trans-membrane a-helices whose hydrophobic length matches the hydrophobic thickness of the lipid bilayer could b e a mechanism of retention in the Golgi apparatus. We have used fluore scence methods to study the interaction of peptides Ac-K-2-G-L-m-W-L-n -K-2-A-amide (Pm+n) with bilayers of phosphatidylcholines with chain l engths between C14 and C24. The peptide P-22 (m = 10, n = 12) incorpor ates into all bilayers, but P-16 (m = 7, n = 9) does not incorporate i nto bilayers when the fatty acyl chain length is C24 and only partly i ncorporates into bilayers where the chain length is C22. The strongest binding is seen when the hydrophobic length of the peptide matches th e calculated hydrophobic thickness of the bilayer. It is suggested tha t a too-thin bilayer can match to a too-long peptide both by stretchin g of the lipid and by tilting of the peptide. However, a too-thick bil ayer can only match a too-thin peptide by compression of the lipid, wh ich becomes energetically unfavorable when the difference between the bilayer thickness and the peptide length exceeds about 10 Angstrom. Th e presence of cholesterol in the bilayer leads to a marked reduction i n the incorporation of Pld into bilayers where the chain length is C18 . Hydrophobic mismatch could explain retention of proteins with short trans-membrane alpha-helical domains in the Golgi, the effect followin g largely from the low concentration of cholesterol in the Golgi membr ane compared to that in the plasma membrane.