title: Hydrophobic mismatch and the incorporation of peptides into lipid bilayers: a possible mechanism for retention in the Golgi.
abstract: Preferential interaction of trans-membrane alpha-helices whose hydrophobic length matches the hydrophobic thickness of the lipid bilayer could be a mechanism of retention in the Golgi apparatus. We have used fluorescence methods to study the interaction of peptides Ac-K2-G-Lm-W-Ln-K2-A-amide (Pm+n) with bilayers of phosphatidylcholines with chain lengths between C14 and C24. The peptide P22 (m = 10, n = 12) incorporates into all bilayers, but P16 (m = 7, n = 9) does not incorporate into bilayers when the fatty acyl chain length is C24 and only partly incorporates into bilayers where the chain length is C22. The strongest binding is seen when the hydrophobic length of the peptide matches the calculated hydrophobic thickness of the bilayer. It is suggested that a too-thin bilayer can match to a too-long peptide both by stretching of the lipid and by tilting of the peptide. However, a too-thick bilayer can only match a too-thin peptide by compression of the lipid, which becomes energetically unfavorable when the difference between the bilayer thickness and the peptide length exceeds about 10 A. The presence of cholesterol in the bilayer leads to a marked reduction in the incorporation of P16 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 following largely from the low concentration of cholesterol in the Golgi membrane compared to that in the plasma membrane.
authors.affiliation: Division of Biochemistry and Molecular Biology, School of Biological Sciences, University of Southampton, Southampton SO16 7PX, U.K.
authors.forename: R J
authors.initials: RJ
authors.lastname: Webb
authors.forename: J M
authors.initials: JM
authors.lastname: East
authors.forename: R P
authors.initials: RP
authors.lastname: Sharma
authors.forename: A G
authors.initials: AG
authors.lastname: Lee
mesh_terms: D002451:Cell Compartmentation; D005089:Exocytosis; D006056:Golgi Apparatus / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism*; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D017433:Protein Structure, Secondary
chemical_list: D008051:Lipid Bilayers; D010455:Peptides; D010743:Phospholipids